Nutrient chapter

Lithium

Lithium is an element whose biological chemistry involves Li+ ions. Food and water supply trace amounts; prescription treatment produces a very different exposure. Lithium carbonate, chloride and orotate remain separate records. A salt's mass is not its elemental lithium mass, and a cell-culture concentration is not an oral dose. Magnesium connects two central branches: lithium can interfere with metal-dependent enzymes, including GSK3 and inositol phosphatases. Inositol recycling changes cell signaling and, in some experiments, protein recycling by autophagy. These observations do not show that lithium strips magnesium from the body or that magnesium supplements predictably reverse its effects. The kidney provides a second network. Sodium channels help lithium enter collecting-duct cells; water-channel changes can impair urine concentration. Sodium intake, sodium loss, fluid loss and interacting medicines change lithium handling. Potassium-deprivation records converge on AQP2 water channels, but that shared target alone does not establish a combined effect. Calcium/PTH regulation and thyroid hormone release provide additional endocrine connections, including the existing potassium-iodide interaction record. Beyond these familiar pathways, the collection connects lithium to PAP clearance and sulfation, cartilage and brain extracellular matrix, citrate transport and lipid synthesis, glycogen storage, neuronal survival, glutamate uptake and circadian clocks. Transporter responses can reverse between species: human and rodent SLC13A5 must not be merged into one supposedly universal effect. The 2025 brain study separates human tissue associations from experimental dietary depletion in mice and lithium-orotate rescue in mouse models. It does not establish a human dietary deficiency threshold or a treatment for dementia. Human cognitive trials retain positive and null findings: the 2026 pilot met none of its six prespecified primary significance thresholds. Differences in exposure, population and outcomes remain visible rather than being turned into a claim of proven prevention. The graph supports discovery questions, not automatic conclusions about synergy or disease causation. Mechanistic records remain source-derived drafts with exact curation spans, primary references and experimental limits. This is a substantial collection, not a claim to capture every possible lithium mechanism.

86 recorded mechanisms · 13 availability situations · 8 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

What the sources say this nutrient does, one relationship at a time. Plain wording comes first; the technical statement follows.

Lithium competitively inhibited mammalian GSK3 with respect to magnesium, but not ATP or substrate.
Lithium ion (Li+) → Mammalian GSK3 preparation in lithium competition assays source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Purified GSK3 kinetic experiments; mammalian and Dictyostelium isoforms.
limitations
The abstract does not resolve every mammalian isoform; no systemic magnesium depletion was measured.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Magnesium availability changes inhibition of a signaling enzyme.
primary_references
Lithium inhibits glycogen synthase kinase-3 by competition for magnesium. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11162580/ · DOI 10.1006/bbrc.2000.4169
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 16–22
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified GSK3 kinetic experiments; mammalian and Dictyostelium isoforms. · source_derived_draft · unverified_draft
## lithium-gsk3-magnesium Magnesium availability changes inhibition of a signaling enzyme. Lithium competitively inhibited mammalian GSK3 with respect to magnesium, but not ATP or substrate. Model: Purified GSK3 kinetic experiments; mammalian and Dictyostelium isoforms. Limitations: The abstract does not resolve every mammalian isoform; no systemic magnesium depletion was measured. Evidence access: Primary abstract Lithium inhibits glycogen synthase kinase-3 by competition for magnesium. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11162580/ · DOI 10.1006/bbrc.2000.4169
Complete structured claim and evidence
ATP concentrations exceeding magnesium progressively inhibited GSK3 in the assay through free-magnesium chelation.
ATP → Mammalian GSK3 preparation in lithium competition assays source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Biochemical concentration titrations.
limitations
This is assay speciation, not evidence that lithium exhausts ATP or that extra magnesium improves clinical outcomes.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
ATP and free magnesium must be considered together.
primary_references
Lithium inhibits glycogen synthase kinase-3 by competition for magnesium. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11162580/ · DOI 10.1006/bbrc.2000.4169
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 24–30
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Biochemical concentration titrations. · source_derived_draft · unverified_draft
## lithium-gsk3-atp-magnesium ATP and free magnesium must be considered together. ATP concentrations exceeding magnesium progressively inhibited GSK3 in the assay through free-magnesium chelation. Model: Biochemical concentration titrations. Limitations: This is assay speciation, not evidence that lithium exhausts ATP or that extra magnesium improves clinical outcomes. Evidence access: Primary abstract Lithium inhibits glycogen synthase kinase-3 by competition for magnesium. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11162580/ · DOI 10.1006/bbrc.2000.4169
Complete structured claim and evidence
Kinetics, modeling and mutagenesis supported a two-metal catalytic model for human inositol monophosphatase.
Mg2+ → IMPA1 (human inositol monophosphatase 1) source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human enzyme structural/kinetic study, including Mn, Zn and Mg titrations.
limitations
Historical mechanistic model; not a universal count for all conformations or family members.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Inositol recycling uses metal-dependent chemistry.
primary_references
Mechanism of inositol monophosphatase, the putative target of lithium therapy. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8016062/ · DOI 10.1073/pnas.91.13.5766
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human enzyme structural/kinetic study, including Mn, Zn and Mg titrations. · source_derived_draft · unverified_draft
## lithium-impa-metal Inositol recycling uses metal-dependent chemistry. Kinetics, modeling and mutagenesis supported a two-metal catalytic model for human inositol monophosphatase. Model: Human enzyme structural/kinetic study, including Mn, Zn and Mg titrations. Limitations: Historical mechanistic model; not a universal count for all conformations or family members. Evidence access: Primary abstract Mechanism of inositol monophosphatase, the putative target of lithium therapy. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8016062/ · DOI 10.1073/pnas.91.13.5766
Complete structured claim and evidence
The human IMPase study supported lithium binding at the second metal site in its catalytic model.
Lithium ion (Li+) → IMPA1 (human inositol monophosphatase 1) source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human enzyme kinetics, fluorescence and structural modeling.
limitations
Binding-site assignment is model-supported; treatment benefit is not established by enzyme inhibition.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Lithium can interrupt the recycling step.
primary_references
Mechanism of inositol monophosphatase, the putative target of lithium therapy. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8016062/ · DOI 10.1073/pnas.91.13.5766
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 40–46
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human enzyme kinetics, fluorescence and structural modeling. · source_derived_draft · unverified_draft
## lithium-impa-lithium Lithium can interrupt the recycling step. The human IMPase study supported lithium binding at the second metal site in its catalytic model. Model: Human enzyme kinetics, fluorescence and structural modeling. Limitations: Binding-site assignment is model-supported; treatment benefit is not established by enzyme inhibition. Evidence access: Primary abstract Mechanism of inositol monophosphatase, the putative target of lithium therapy. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8016062/ · DOI 10.1073/pnas.91.13.5766
Complete structured claim and evidence
Purified calf-brain INPP1 showed cooperative magnesium dependence, with half-maximal stimulation near 0.3 mM.
Mg2+ → Bovine inositol polyphosphate 1-phosphatase / INPP1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Calf-brain enzyme purification and kinetics.
limitations
In-vitro cofactor concentration is not a human blood target.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
A second recycling enzyme also depends on magnesium.
primary_references
Inositol polyphosphate 1-phosphatase from calf brain. Purification and inhibition by Li+, Ca2+, and Mn2+. · 1987 · https://pubmed.ncbi.nlm.nih.gov/2824473/
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 48–54
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Calf-brain enzyme purification and kinetics. · source_derived_draft · unverified_draft
## lithium-inpp1-magnesium A second recycling enzyme also depends on magnesium. Purified calf-brain INPP1 showed cooperative magnesium dependence, with half-maximal stimulation near 0.3 mM. Model: Calf-brain enzyme purification and kinetics. Limitations: In-vitro cofactor concentration is not a human blood target. Evidence access: Primary abstract Inositol polyphosphate 1-phosphatase from calf brain. Purification and inhibition by Li+, Ca2+, and Mn2+. · 1987 · https://pubmed.ncbi.nlm.nih.gov/2824473/
Complete structured claim and evidence
Lithium inhibited bovine INPP1 differently by substrate: Ki about 6 mM for Ins(1,4)P2 versus 0.5–1 mM for Ins(1,3,4)P3.
Lithium ion (Li+) → Bovine inositol polyphosphate 1-phosphatase / INPP1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Purified calf-brain INPP1.
limitations
Do not substitute signaling IP3, Ins(1,4,5)P3, for the distinct Ins(1,3,4)P3 substrate.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
The same enzyme can respond differently depending on its substrate.
primary_references
Inositol polyphosphate 1-phosphatase from calf brain. Purification and inhibition by Li+, Ca2+, and Mn2+. · 1987 · https://pubmed.ncbi.nlm.nih.gov/2824473/
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 56–62
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified calf-brain INPP1. · source_derived_draft · unverified_draft
## lithium-inpp1-substrate-specific The same enzyme can respond differently depending on its substrate. Lithium inhibited bovine INPP1 differently by substrate: Ki about 6 mM for Ins(1,4)P2 versus 0.5–1 mM for Ins(1,3,4)P3. Model: Purified calf-brain INPP1. Limitations: Do not substitute signaling IP3, Ins(1,4,5)P3, for the distinct Ins(1,3,4)P3 substrate. Evidence access: Primary abstract Inositol polyphosphate 1-phosphatase from calf brain. Purification and inhibition by Li+, Ca2+, and Mn2+. · 1987 · https://pubmed.ncbi.nlm.nih.gov/2824473/
Complete structured claim and evidence
Calcium and manganese each inhibited the calf-brain enzyme by about half near 6 micromolar under the reported assay conditions.
Calcium ion → Bovine inositol polyphosphate 1-phosphatase / INPP1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Purified calf-brain enzyme.
limitations
Free-ion assay concentrations do not establish dietary antagonism.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
A mineral that activates one enzyme can inhibit another.
primary_references
Inositol polyphosphate 1-phosphatase from calf brain. Purification and inhibition by Li+, Ca2+, and Mn2+. · 1987 · https://pubmed.ncbi.nlm.nih.gov/2824473/
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 64–70
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified calf-brain enzyme. · source_derived_draft · unverified_draft
## lithium-inpp1-calcium-manganese A mineral that activates one enzyme can inhibit another. Calcium and manganese each inhibited the calf-brain enzyme by about half near 6 micromolar under the reported assay conditions. Model: Purified calf-brain enzyme. Limitations: Free-ion assay concentrations do not establish dietary antagonism. Evidence access: Primary abstract Inositol polyphosphate 1-phosphatase from calf brain. Purification and inhibition by Li+, Ca2+, and Mn2+. · 1987 · https://pubmed.ncbi.nlm.nih.gov/2824473/
Complete structured claim and evidence
Lithium treatment increased mono/bis-phosphorylated inositol species in COS-7 cells, consistent with inhibited recycling.
Lithium ion (Li+) → Inositol monophosphates source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Monkey COS-7 cells; 10 mM LiCl, 24-hour metabolite assay.
limitations
Combined IP1–2 measurement; this exposure exceeds typical clinical serum concentrations.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Blocking recycling lets upstream material accumulate.
primary_references
Lithium induces autophagy by inhibiting inositol monophosphatase. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16186256/ · DOI 10.1083/jcb.200504035
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 72–78
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Monkey COS-7 cells; 10 mM LiCl, 24-hour metabolite assay. · source_derived_draft · unverified_draft
## lithium-inositol-phosphate-accumulation Blocking recycling lets upstream material accumulate. Lithium treatment increased mono/bis-phosphorylated inositol species in COS-7 cells, consistent with inhibited recycling. Model: Monkey COS-7 cells; 10 mM LiCl, 24-hour metabolite assay. Limitations: Combined IP1–2 measurement; this exposure exceeds typical clinical serum concentrations. Evidence access: Primary full text Lithium induces autophagy by inhibiting inositol monophosphatase. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16186256/ · DOI 10.1083/jcb.200504035
Complete structured claim and evidence
Lithium lowered IP3 in the COS-7 experiments; added myo-inositol raised it relative to lithium alone.
Lithium ion (Li+) → IP3 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Monkey COS-7; 10 mM LiCl, 1 mM myo-inositol rescue.
limitations
Cell-culture rescue is not a clinical supplement recommendation.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Availability of the precursor changes a signaling messenger.
primary_references
Lithium induces autophagy by inhibiting inositol monophosphatase. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16186256/ · DOI 10.1083/jcb.200504035
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 80–86
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Monkey COS-7; 10 mM LiCl, 1 mM myo-inositol rescue. · source_derived_draft · unverified_draft
## lithium-ip3-decrease Availability of the precursor changes a signaling messenger. Lithium lowered IP3 in the COS-7 experiments; added myo-inositol raised it relative to lithium alone. Model: Monkey COS-7; 10 mM LiCl, 1 mM myo-inositol rescue. Limitations: Cell-culture rescue is not a clinical supplement recommendation. Evidence access: Primary full text Lithium induces autophagy by inhibiting inositol monophosphatase. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16186256/ · DOI 10.1083/jcb.200504035
Complete structured claim and evidence
Lithium increased autophagy markers through an IMPase-linked route without the mTOR inhibition detected with rapamycin.
Lithium ion (Li+) → Monkey COS-7-cell lithium-associated autophagy source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Monkey COS-7; 10 mM LiCl, LC3 and pathway assays.
limitations
Not evidence that every lithium exposure increases completed autophagic flux or human longevity.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Cellular recycling can change through a route outside mTOR.
primary_references
Lithium induces autophagy by inhibiting inositol monophosphatase. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16186256/ · DOI 10.1083/jcb.200504035
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 88–94
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Monkey COS-7; 10 mM LiCl, LC3 and pathway assays. · source_derived_draft · unverified_draft
## lithium-autophagy Cellular recycling can change through a route outside mTOR. Lithium increased autophagy markers through an IMPase-linked route without the mTOR inhibition detected with rapamycin. Model: Monkey COS-7; 10 mM LiCl, LC3 and pathway assays. Limitations: Not evidence that every lithium exposure increases completed autophagic flux or human longevity. Evidence access: Primary full text Lithium induces autophagy by inhibiting inositol monophosphatase. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16186256/ · DOI 10.1083/jcb.200504035
Complete structured claim and evidence
Lithium accelerated clearance of expressed mutant huntingtin and alpha-synuclein in inducible PC12 models.
Lithium ion (Li+) → Rat PC12-cell clearance of expressed mutant proteins source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Rat PC12; 10 mM LiCl; expression switched off before clearance measurement.
limitations
Engineered protein models do not establish treatment of Huntington or Parkinson disease.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Recycling changed the persistence of aggregation-prone proteins.
primary_references
Lithium induces autophagy by inhibiting inositol monophosphatase. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16186256/ · DOI 10.1083/jcb.200504035
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 96–102
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat PC12; 10 mM LiCl; expression switched off before clearance measurement. · source_derived_draft · unverified_draft
## lithium-protein-clearance Recycling changed the persistence of aggregation-prone proteins. Lithium accelerated clearance of expressed mutant huntingtin and alpha-synuclein in inducible PC12 models. Model: Rat PC12; 10 mM LiCl; expression switched off before clearance measurement. Limitations: Engineered protein models do not establish treatment of Huntington or Parkinson disease. Evidence access: Primary full text Lithium induces autophagy by inhibiting inositol monophosphatase. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16186256/ · DOI 10.1083/jcb.200504035
Complete structured claim and evidence
Added myo-inositol attenuated lithium-enhanced mutant-protein clearance in PC12 cells.
Myo-inositol → Rat PC12-cell clearance of expressed mutant proteins source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Rat PC12; 1 mM myo-inositol with 10 mM LiCl.
limitations
Time-dependent and incomplete effects; not proof that oral inositol reverses mood stabilization.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
A connected nutrient can counter an experimentally induced response.
primary_references
Lithium induces autophagy by inhibiting inositol monophosphatase. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16186256/ · DOI 10.1083/jcb.200504035
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 104–110
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat PC12; 1 mM myo-inositol with 10 mM LiCl. · source_derived_draft · unverified_draft
## lithium-inositol-rescue A connected nutrient can counter an experimentally induced response. Added myo-inositol attenuated lithium-enhanced mutant-protein clearance in PC12 cells. Model: Rat PC12; 1 mM myo-inositol with 10 mM LiCl. Limitations: Time-dependent and incomplete effects; not proof that oral inositol reverses mood stabilization. Evidence access: Primary full text Lithium induces autophagy by inhibiting inositol monophosphatase. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16186256/ · DOI 10.1083/jcb.200504035
Complete structured claim and evidence
Cloned rat RnPIP hydrolyzed PAP and Ins(1,4)P2 in magnesium-dependent reactions.
Rat bisphosphate nucleotidase 1 / RnPIP → 3-prime-Phosphoadenosine-5-prime-phosphate / PAP source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Cloned rat enzyme; biochemical substrate assays.
limitations
The paper proposes consequences for sulfotransferases/RNA processing; those downstream effects were not all tested.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Clearing a sulfur-pathway by-product uses another metal-dependent enzyme.
primary_references
A novel mammalian lithium-sensitive enzyme with a dual enzymatic activity, 3'-phosphoadenosine 5'-phosphate phosphatase and inositol-polyphosphate 1-phosphatase. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10347153/ · DOI 10.1074/jbc.274.23.16034
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cloned rat enzyme; biochemical substrate assays. · source_derived_draft · unverified_draft
## lithium-bpnt1-substrate Clearing a sulfur-pathway by-product uses another metal-dependent enzyme. Cloned rat RnPIP hydrolyzed PAP and Ins(1,4)P2 in magnesium-dependent reactions. Model: Cloned rat enzyme; biochemical substrate assays. Limitations: The paper proposes consequences for sulfotransferases/RNA processing; those downstream effects were not all tested. Evidence access: Primary abstract A novel mammalian lithium-sensitive enzyme with a dual enzymatic activity, 3'-phosphoadenosine 5'-phosphate phosphatase and inositol-polyphosphate 1-phosphatase. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10347153/ · DOI 10.1074/jbc.274.23.16034
Complete structured claim and evidence
Submillimolar lithium chloride inhibited rat RnPIP hydrolysis of both PAP and Ins(1,4)P2.
Lithium ion (Li+) → Rat bisphosphate nucleotidase 1 / RnPIP source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Rat recombinant enzyme; calcium also inhibited activity.
limitations
Not a quantitative human exposure-to-organ-injury model.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
One lithium-sensitive enzyme connects two metabolic branches.
primary_references
A novel mammalian lithium-sensitive enzyme with a dual enzymatic activity, 3'-phosphoadenosine 5'-phosphate phosphatase and inositol-polyphosphate 1-phosphatase. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10347153/ · DOI 10.1074/jbc.274.23.16034
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat recombinant enzyme; calcium also inhibited activity. · source_derived_draft · unverified_draft
## lithium-bpnt1-lithium One lithium-sensitive enzyme connects two metabolic branches. Submillimolar lithium chloride inhibited rat RnPIP hydrolysis of both PAP and Ins(1,4)P2. Model: Rat recombinant enzyme; calcium also inhibited activity. Limitations: Not a quantitative human exposure-to-organ-injury model. Evidence access: Primary abstract A novel mammalian lithium-sensitive enzyme with a dual enzymatic activity, 3'-phosphoadenosine 5'-phosphate phosphatase and inositol-polyphosphate 1-phosphatase. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10347153/ · DOI 10.1074/jbc.274.23.16034
Complete structured claim and evidence
Bpnt1 knockout raised mouse liver PAP up to about 50-fold.
Mouse bisphosphate nucleotidase 1 / Bpnt1 → 3-prime-Phosphoadenosine-5-prime-phosphate / PAP source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Constitutive Bpnt1 knockout mice.
limitations
Genetic absence is not equivalent to dietary lithium exposure or partial drug inhibition.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Loss of clearance lets the by-product build up.
primary_references
Role for cytoplasmic nucleotide hydrolysis in hepatic function and protein synthesis. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23479625/ · DOI 10.1073/pnas.1205001110
trigger_kind
machinery_impairment Imported condition classification; unverified.
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Constitutive Bpnt1 knockout mice. · source_derived_draft · unverified_draft
## lithium-bpnt1-loss-pap Loss of clearance lets the by-product build up. Bpnt1 knockout raised mouse liver PAP up to about 50-fold. Model: Constitutive Bpnt1 knockout mice. Limitations: Genetic absence is not equivalent to dietary lithium exposure or partial drug inhibition. Evidence access: Primary abstract Role for cytoplasmic nucleotide hydrolysis in hepatic function and protein synthesis. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23479625/ · DOI 10.1073/pnas.1205001110
Complete structured claim and evidence
Bpnt1-deficient mice showed repressed translation, abnormal nucleoli and liver injury.
Mouse bisphosphate nucleotidase 1 / Bpnt1 → Mouse hepatic protein synthesis source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse knockout; tissue-dependent phenotype.
limitations
Not evidence that routine lithium treatment causes this knockout syndrome.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
The accumulated by-product accompanied a failure of protein production.
primary_references
Role for cytoplasmic nucleotide hydrolysis in hepatic function and protein synthesis. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23479625/ · DOI 10.1073/pnas.1205001110
trigger_kind
machinery_impairment Imported condition classification; unverified.
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse knockout; tissue-dependent phenotype. · source_derived_draft · unverified_draft
## lithium-bpnt1-loss-translation The accumulated by-product accompanied a failure of protein production. Bpnt1-deficient mice showed repressed translation, abnormal nucleoli and liver injury. Model: Mouse knockout; tissue-dependent phenotype. Limitations: Not evidence that routine lithium treatment causes this knockout syndrome. Evidence access: Primary abstract Role for cytoplasmic nucleotide hydrolysis in hepatic function and protein synthesis. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23479625/ · DOI 10.1073/pnas.1205001110
Complete structured claim and evidence
Reducing PAP synthesis genetically rescued the Bpnt1-knockout phenotype.
Reduced PAP synthesis in double-mutant mice → Mouse hepatic protein synthesis source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse double-mutant genetic experiment.
limitations
Does not justify sulfur restriction; a pathway perturbation is not a nutritional prescription.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Reducing what enters a blocked pathway can rescue its consequences.
primary_references
Role for cytoplasmic nucleotide hydrolysis in hepatic function and protein synthesis. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23479625/ · DOI 10.1073/pnas.1205001110
trigger_kind
machinery_impairment Imported condition classification; unverified.
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse double-mutant genetic experiment. · source_derived_draft · unverified_draft
## lithium-pap-synthesis-rescue Reducing what enters a blocked pathway can rescue its consequences. Reducing PAP synthesis genetically rescued the Bpnt1-knockout phenotype. Model: Mouse double-mutant genetic experiment. Limitations: Does not justify sulfur restriction; a pathway perturbation is not a nutritional prescription. Evidence access: Primary abstract Role for cytoplasmic nucleotide hydrolysis in hepatic function and protein synthesis. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23479625/ · DOI 10.1073/pnas.1205001110
Complete structured claim and evidence
Wild-type Bpnt2 restored GAG sulfation in knockout fibroblasts; catalytic-dead D108A did not.
Mouse Golgi bisphosphate nucleotidase 2 / Bpnt2 → Mouse fibroblast glycosaminoglycan sulfation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Mouse embryonic fibroblast pellets; complementation and sulfation assays.
limitations
Sulfation depends on compartment and substrate; not a universal human sulfur requirement.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
The enzyme must work, not merely be present.
primary_references
Sulfation of glycosaminoglycans depends on the catalytic activity of lithium-inhibited phosphatase BPNT2 in vitro. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34634304/ · DOI 10.1016/j.jbc.2021.101293
trigger_kind
machinery_impairment Imported condition classification; unverified.
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse embryonic fibroblast pellets; complementation and sulfation assays. · source_derived_draft · unverified_draft
## lithium-bpnt2-catalysis The enzyme must work, not merely be present. Wild-type Bpnt2 restored GAG sulfation in knockout fibroblasts; catalytic-dead D108A did not. Model: Mouse embryonic fibroblast pellets; complementation and sulfation assays. Limitations: Sulfation depends on compartment and substrate; not a universal human sulfur requirement. Evidence access: Primary full text Sulfation of glycosaminoglycans depends on the catalytic activity of lithium-inhibited phosphatase BPNT2 in vitro. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34634304/ · DOI 10.1016/j.jbc.2021.101293
Complete structured claim and evidence
LiCl reduced intracellular and secreted GAG sulfation in wild-type mouse fibroblasts, with no further reduction after Bpnt2 knockout.
Lithium ion (Li+) → Mouse fibroblast glycosaminoglycan sulfation source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Mouse embryonic fibroblasts; 10 mM LiCl versus matched NaCl.
limitations
High experimental exposure; knockout occlusion supports a pathway but does not prove clinical cartilage damage.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
The lithium response depended on this Golgi enzyme.
primary_references
Sulfation of glycosaminoglycans depends on the catalytic activity of lithium-inhibited phosphatase BPNT2 in vitro. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34634304/ · DOI 10.1016/j.jbc.2021.101293
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse embryonic fibroblasts; 10 mM LiCl versus matched NaCl. · source_derived_draft · unverified_draft
## lithium-bpnt2-lithium-gag The lithium response depended on this Golgi enzyme. LiCl reduced intracellular and secreted GAG sulfation in wild-type mouse fibroblasts, with no further reduction after Bpnt2 knockout. Model: Mouse embryonic fibroblasts; 10 mM LiCl versus matched NaCl. Limitations: High experimental exposure; knockout occlusion supports a pathway but does not prove clinical cartilage damage. Evidence access: Primary full text Sulfation of glycosaminoglycans depends on the catalytic activity of lithium-inhibited phosphatase BPNT2 in vitro. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34634304/ · DOI 10.1016/j.jbc.2021.101293
Complete structured claim and evidence
Nervous-system Bpnt2 deletion lowered chondroitin-4-sulfation and increased chondroitin-6-sulfation in selected brain regions.
Mouse Golgi bisphosphate nucleotidase 2 / Bpnt2 → Mouse cortical and hippocampal chondroitin sulfation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Nestin-Cre conditional mouse knockout.
limitations
No significant gross perineuronal-net or tested behavioral abnormalities were detected; not a lithium treatment experiment.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
This enzyme also changes the brain extracellular matrix.
primary_references
Bisphosphate nucleotidase 2 (BPNT2), a molecular target of lithium, regulates chondroitin sulfation patterns in the cerebral cortex and hippocampus. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34920982/ · DOI 10.1016/j.jbior.2021.100858
trigger_kind
machinery_impairment Imported condition classification; unverified.
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Nestin-Cre conditional mouse knockout. · source_derived_draft · unverified_draft
## lithium-bpnt2-brain-loss This enzyme also changes the brain extracellular matrix. Nervous-system Bpnt2 deletion lowered chondroitin-4-sulfation and increased chondroitin-6-sulfation in selected brain regions. Model: Nestin-Cre conditional mouse knockout. Limitations: No significant gross perineuronal-net or tested behavioral abnormalities were detected; not a lithium treatment experiment. Evidence access: Primary abstract Bisphosphate nucleotidase 2 (BPNT2), a molecular target of lithium, regulates chondroitin sulfation patterns in the cerebral cortex and hippocampus. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34920982/ · DOI 10.1016/j.jbior.2021.100858
Complete structured claim and evidence
Lithium reduced tau phosphorylation through reversible GSK3 inhibition in human NT2N neurons.
Lithium ion (Li+) → Human microtubule-associated protein tau / MAPT source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Cultured human NT2N neurons.
limitations
Does not demonstrate dementia prevention in people.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
A signaling enzyme changes chemical marks on a structural protein.
primary_references
Lithium reduces tau phosphorylation by inhibition of glycogen synthase kinase-3. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9312151/ · DOI 10.1074/jbc.272.40.25326
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cultured human NT2N neurons. · source_derived_draft · unverified_draft
## lithium-tau-phosphorylation A signaling enzyme changes chemical marks on a structural protein. Lithium reduced tau phosphorylation through reversible GSK3 inhibition in human NT2N neurons. Model: Cultured human NT2N neurons. Limitations: Does not demonstrate dementia prevention in people. Evidence access: Primary abstract Lithium reduces tau phosphorylation by inhibition of glycogen synthase kinase-3. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9312151/ · DOI 10.1074/jbc.272.40.25326
Complete structured claim and evidence
Lithium increased tau–microtubule binding and microtubule assembly in the NT2N study.
Lithium ion (Li+) → Human NT2N tau binding to microtubules source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human neuron-like cell culture.
limitations
Same paper as the tau-phosphorylation result, not independent replication.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
The altered protein interacted more strongly with the cellular scaffold.
primary_references
Lithium reduces tau phosphorylation by inhibition of glycogen synthase kinase-3. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9312151/ · DOI 10.1074/jbc.272.40.25326
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human neuron-like cell culture. · source_derived_draft · unverified_draft
## lithium-tau-microtubules The altered protein interacted more strongly with the cellular scaffold. Lithium increased tau–microtubule binding and microtubule assembly in the NT2N study. Model: Human neuron-like cell culture. Limitations: Same paper as the tau-phosphorylation result, not independent replication. Evidence access: Primary abstract Lithium reduces tau phosphorylation by inhibition of glycogen synthase kinase-3. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9312151/ · DOI 10.1074/jbc.272.40.25326
Complete structured claim and evidence
Lithium disrupted a beta-arrestin2–Akt–PP2A complex and altered Akt/GSK3 signaling in mice.
Lithium ion (Li+) → Mouse beta-arrestin2–Akt–PP2A signaling complex source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse pharmacology and biochemical complex assays.
limitations
A second pathway alongside direct enzyme inhibition, not a complete explanation of mood stabilization.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Lithium can change how signaling proteins assemble.
primary_references
A beta-arrestin 2 signaling complex mediates lithium action on behavior. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18191226/ · DOI 10.1016/j.cell.2007.11.041
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse pharmacology and biochemical complex assays. · source_derived_draft · unverified_draft
## lithium-arrestin-complex Lithium can change how signaling proteins assemble. Lithium disrupted a beta-arrestin2–Akt–PP2A complex and altered Akt/GSK3 signaling in mice. Model: Mouse pharmacology and biochemical complex assays. Limitations: A second pathway alongside direct enzyme inhibition, not a complete explanation of mood stabilization. Evidence access: Primary abstract A beta-arrestin 2 signaling complex mediates lithium action on behavior. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18191226/ · DOI 10.1016/j.cell.2007.11.041
Complete structured claim and evidence
Arrb2 knockout prevented the reported lithium effects on Akt/GSK3 signaling and associated mouse behaviors.
Mouse beta-arrestin 2 / Arrb2 → Mouse beta-arrestin2–Akt–PP2A signaling complex source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse Arrb2 knockout comparison.
limitations
Does not abolish every molecular lithium effect.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Removing the scaffold removed this lithium response.
primary_references
A beta-arrestin 2 signaling complex mediates lithium action on behavior. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18191226/ · DOI 10.1016/j.cell.2007.11.041
trigger_kind
machinery_impairment Imported condition classification; unverified.
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse Arrb2 knockout comparison. · source_derived_draft · unverified_draft
## lithium-arrestin-loss Removing the scaffold removed this lithium response. Arrb2 knockout prevented the reported lithium effects on Akt/GSK3 signaling and associated mouse behaviors. Model: Mouse Arrb2 knockout comparison. Limitations: Does not abolish every molecular lithium effect. Evidence access: Primary abstract A beta-arrestin 2 signaling complex mediates lithium action on behavior. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18191226/ · DOI 10.1016/j.cell.2007.11.041
Complete structured claim and evidence
Lithium increased cellular BDNF in rat cortical neurons after three days.
Lithium ion (Li+) → Rat brain-derived neurotrophic factor / Bdnf source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Rat primary cortical neurons; companion excitotoxicity experiments.
limitations
Time-dependent culture finding; not guaranteed human blood BDNF elevation.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
A survival-supporting signal rose over days.
primary_references
Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons: an essential step for neuroprotection against glutamate excitotoxicity. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12504924/ · DOI 10.1016/s0028-3908(02)00217-4
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat primary cortical neurons; companion excitotoxicity experiments. · source_derived_draft · unverified_draft
## lithium-bdnf-induction A survival-supporting signal rose over days. Lithium increased cellular BDNF in rat cortical neurons after three days. Model: Rat primary cortical neurons; companion excitotoxicity experiments. Limitations: Time-dependent culture finding; not guaranteed human blood BDNF elevation. Evidence access: Primary abstract Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons: an essential step for neuroprotection against glutamate excitotoxicity. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12504924/ · DOI 10.1016/s0028-3908(02)00217-4
Complete structured claim and evidence
Lithium increased TrkB Tyr490 phosphorylation after five days in rat cortical cultures.
Lithium ion (Li+) → Rat TrkB receptor / Ntrk2 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Rat primary cortical neurons.
limitations
Pathway interpretation supported by inhibitor and antibody experiments; not direct lithium binding to TrkB.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
The BDNF receptor became more active after a delay.
primary_references
Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons: an essential step for neuroprotection against glutamate excitotoxicity. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12504924/ · DOI 10.1016/s0028-3908(02)00217-4
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat primary cortical neurons. · source_derived_draft · unverified_draft
## lithium-trkb-activation The BDNF receptor became more active after a delay. Lithium increased TrkB Tyr490 phosphorylation after five days in rat cortical cultures. Model: Rat primary cortical neurons. Limitations: Pathway interpretation supported by inhibitor and antibody experiments; not direct lithium binding to TrkB. Evidence access: Primary abstract Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons: an essential step for neuroprotection against glutamate excitotoxicity. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12504924/ · DOI 10.1016/s0028-3908(02)00217-4
Complete structured claim and evidence
Lithium failed to protect cortical neurons from Bdnf heterozygous or homozygous knockout mice against glutamate toxicity.
Mouse brain-derived neurotrophic factor / Bdnf → Mouse cortical-neuron survival during glutamate challenge source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse knockout-derived primary neurons versus wild-type littermates.
limitations
Genetic failure is not a dietary BDNF deficiency or human therapeutic test.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
The protective response required intact survival machinery.
primary_references
Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons: an essential step for neuroprotection against glutamate excitotoxicity. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12504924/ · DOI 10.1016/s0028-3908(02)00217-4
trigger_kind
machinery_impairment Imported condition classification; unverified.
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse knockout-derived primary neurons versus wild-type littermates. · source_derived_draft · unverified_draft
## lithium-bdnf-loss The protective response required intact survival machinery. Lithium failed to protect cortical neurons from Bdnf heterozygous or homozygous knockout mice against glutamate toxicity. Model: Mouse knockout-derived primary neurons versus wild-type littermates. Limitations: Genetic failure is not a dietary BDNF deficiency or human therapeutic test. Evidence access: Primary abstract Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons: an essential step for neuroprotection against glutamate excitotoxicity. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12504924/ · DOI 10.1016/s0028-3908(02)00217-4
Complete structured claim and evidence
Acute lithium exposure lowered glutamate-uptake capacity in mouse cortical preparations without changing apparent substrate affinity.
Lithium ion (Li+) → Mouse cortical presynaptic glutamate uptake source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Cortical slices and synaptosomes; concentration-response experiments.
limitations
Do not merge acute addition with chronic in-vivo treatment.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
An immediate effect can differ from long-term adaptation.
primary_references
Lithium acutely inhibits and chronically up-regulates and stabilizes glutamate uptake by presynaptic nerve endings in mouse cerebral cortex. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9653192/ · DOI 10.1073/pnas.95.14.8363
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cortical slices and synaptosomes; concentration-response experiments. · source_derived_draft · unverified_draft
## lithium-glutamate-acute An immediate effect can differ from long-term adaptation. Acute lithium exposure lowered glutamate-uptake capacity in mouse cortical preparations without changing apparent substrate affinity. Model: Cortical slices and synaptosomes; concentration-response experiments. Limitations: Do not merge acute addition with chronic in-vivo treatment. Evidence access: Primary abstract Lithium acutely inhibits and chronically up-regulates and stabilizes glutamate uptake by presynaptic nerve endings in mouse cerebral cortex. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9653192/ · DOI 10.1073/pnas.95.14.8363
Complete structured claim and evidence
Chronic lithium treatment increased synaptosomal glutamate uptake in mice at a reported blood lithium level of 0.7 mM.
Lithium ion (Li+) → Mouse cortical presynaptic glutamate uptake source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mice treated in vivo, followed by synaptosome assays.
limitations
A duration-dependent difference explained in the same paper, not an unresolved contradiction.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Longer exposure produced an opposite uptake response.
primary_references
Lithium acutely inhibits and chronically up-regulates and stabilizes glutamate uptake by presynaptic nerve endings in mouse cerebral cortex. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9653192/ · DOI 10.1073/pnas.95.14.8363
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mice treated in vivo, followed by synaptosome assays. · source_derived_draft · unverified_draft
## lithium-glutamate-chronic Longer exposure produced an opposite uptake response. Chronic lithium treatment increased synaptosomal glutamate uptake in mice at a reported blood lithium level of 0.7 mM. Model: Mice treated in vivo, followed by synaptosome assays. Limitations: A duration-dependent difference explained in the same paper, not an unresolved contradiction. Evidence access: Primary abstract Lithium acutely inhibits and chronically up-regulates and stabilizes glutamate uptake by presynaptic nerve endings in mouse cerebral cortex. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9653192/ · DOI 10.1073/pnas.95.14.8363
Complete structured claim and evidence
Lithium effects on circadian rhythms varied across bipolar patient-derived fibroblasts; longer-period cells had muted responses.
Lithium ion (Li+) → Human fibroblast circadian response to lithium source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
39 bipolar donors and 23 controls; ex-vivo clock measurements.
limitations
Not a validated clinical test for choosing treatment.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Cells from different people did not respond identically.
primary_references
Patient fibroblast circadian rhythms predict lithium sensitivity in bipolar disorder. · 2021 · https://pubmed.ncbi.nlm.nih.gov/32404948/ · DOI 10.1038/s41380-020-0769-6
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 39 bipolar donors and 23 controls; ex-vivo clock measurements. · source_derived_draft · unverified_draft
## lithium-clock-person-specific Cells from different people did not respond identically. Lithium effects on circadian rhythms varied across bipolar patient-derived fibroblasts; longer-period cells had muted responses. Model: 39 bipolar donors and 23 controls; ex-vivo clock measurements. Limitations: Not a validated clinical test for choosing treatment. Evidence access: Primary full text Patient fibroblast circadian rhythms predict lithium sensitivity in bipolar disorder. · 2021 · https://pubmed.ncbi.nlm.nih.gov/32404948/ · DOI 10.1038/s41380-020-0769-6
Complete structured claim and evidence
Lithium-associated period lengthening accompanied altered SCN GSK3 expression and phosphorylation in mice.
Lithium ion (Li+) → Mouse locomotor circadian period source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse locomotor monitoring and suprachiasmatic-nucleus assays.
limitations
Association does not establish that GSK3 is the sole circadian target.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
A brain clock and its signaling proteins changed together.
primary_references
Effect of lithium on the circadian rhythms of locomotor activity and glycogen synthase kinase-3 protein expression in the mouse suprachiasmatic nuclei. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15090054/ · DOI 10.1111/j.0953-816X.2004.03322.x
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse locomotor monitoring and suprachiasmatic-nucleus assays. · source_derived_draft · unverified_draft
## lithium-clock-mouse A brain clock and its signaling proteins changed together. Lithium-associated period lengthening accompanied altered SCN GSK3 expression and phosphorylation in mice. Model: Mouse locomotor monitoring and suprachiasmatic-nucleus assays. Limitations: Association does not establish that GSK3 is the sole circadian target. Evidence access: Primary abstract Effect of lithium on the circadian rhythms of locomotor activity and glycogen synthase kinase-3 protein expression in the mouse suprachiasmatic nuclei. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15090054/ · DOI 10.1111/j.0953-816X.2004.03322.x
Complete structured claim and evidence
Lithium stimulated human NaCT-mediated citrate transport at concentrations relevant to prescription exposure.
Lithium ion (Li+) → Human sodium-coupled citrate transporter / SLC13A5 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Expressed human transporter and human liver-cell experiments.
limitations
Not evidence that trace lithium has the same effect or that citrate salt ingestion determines the response.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
A sodium-coupled carrier links lithium to carbon metabolism.
primary_references
Human sodium-coupled citrate transporter, the orthologue of Drosophila Indy, as a novel target for lithium action. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12826022/ · DOI 10.1042/BJ20030827
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Expressed human transporter and human liver-cell experiments. · source_derived_draft · unverified_draft
## lithium-nact-human A sodium-coupled carrier links lithium to carbon metabolism. Lithium stimulated human NaCT-mediated citrate transport at concentrations relevant to prescription exposure. Model: Expressed human transporter and human liver-cell experiments. Limitations: Not evidence that trace lithium has the same effect or that citrate salt ingestion determines the response. Evidence access: Primary abstract Human sodium-coupled citrate transporter, the orthologue of Drosophila Indy, as a novel target for lithium action. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12826022/ · DOI 10.1042/BJ20030827
Complete structured claim and evidence
Lithium increased NaCT-mediated use of extracellular citrate for lipid synthesis in human liver cells.
Human sodium-coupled citrate transporter / SLC13A5 → Human liver-cell extracellular-citrate incorporation into lipids source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human liver-cell tracer/transport study.
limitations
Does not establish that this pathway explains clinical weight change.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Transported citrate can enter lipid-building pathways.
primary_references
Human sodium-coupled citrate transporter, the orthologue of Drosophila Indy, as a novel target for lithium action. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12826022/ · DOI 10.1042/BJ20030827
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human liver-cell tracer/transport study. · source_derived_draft · unverified_draft
## lithium-nact-lipids Transported citrate can enter lipid-building pathways. Lithium increased NaCT-mediated use of extracellular citrate for lipid synthesis in human liver cells. Model: Human liver-cell tracer/transport study. Limitations: Does not establish that this pathway explains clinical weight change. Evidence access: Primary abstract Human sodium-coupled citrate transporter, the orthologue of Drosophila Indy, as a novel target for lithium action. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12826022/ · DOI 10.1042/BJ20030827
Complete structured claim and evidence
Lithium inhibited rat NaCT while stimulating primate transporters in the same comparative study.
Lithium ion (Li+) → Rat sodium-coupled citrate transporter / Slc13a5 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Transporters cloned from eight species.
limitations
Explicit species difference; no contradiction between correctly scoped records.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
The human result cannot be assumed in rodents.
primary_references
Species-specific influence of lithium on the activity of SLC13A5 (NaCT): lithium-induced activation is specific for the transporter in primates. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25617245/ · DOI 10.1124/jpet.114.221523
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Transporters cloned from eight species. · source_derived_draft · unverified_draft
## lithium-nact-rat The human result cannot be assumed in rodents. Lithium inhibited rat NaCT while stimulating primate transporters in the same comparative study. Model: Transporters cloned from eight species. Limitations: Explicit species difference; no contradiction between correctly scoped records. Evidence access: Primary abstract Species-specific influence of lithium on the activity of SLC13A5 (NaCT): lithium-induced activation is specific for the transporter in primates. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25617245/ · DOI 10.1124/jpet.114.221523
Complete structured claim and evidence
Lithium shifted human NaCT toward higher substrate affinity and lower transport capacity.
Lithium ion (Li+) → Human sodium-coupled citrate transporter / SLC13A5 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Cloned human transporter kinetic analysis.
limitations
Net flux depends on citrate and ion concentrations; not unconditional stimulation at every substrate level.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
A stronger apparent response can coexist with a lower maximum rate.
primary_references
Species-specific influence of lithium on the activity of SLC13A5 (NaCT): lithium-induced activation is specific for the transporter in primates. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25617245/ · DOI 10.1124/jpet.114.221523
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cloned human transporter kinetic analysis. · source_derived_draft · unverified_draft
## lithium-nact-affinity A stronger apparent response can coexist with a lower maximum rate. Lithium shifted human NaCT toward higher substrate affinity and lower transport capacity. Model: Cloned human transporter kinetic analysis. Limitations: Net flux depends on citrate and ion concentrations; not unconditional stimulation at every substrate level. Evidence access: Primary abstract Species-specific influence of lithium on the activity of SLC13A5 (NaCT): lithium-induced activation is specific for the transporter in primates. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25617245/ · DOI 10.1124/jpet.114.221523
Complete structured claim and evidence
F500W increased baseline transport but nearly eliminated additional lithium stimulation of human NaCT.
Human SLC13A5 F500W variant → Human sodium-coupled citrate transporter / SLC13A5 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Site-directed human transporter mutagenesis.
limitations
Engineered variant, not evidence of a common human nutritional phenotype.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
A protein variant can change responsiveness independently of intake.
primary_references
Species-specific influence of lithium on the activity of SLC13A5 (NaCT): lithium-induced activation is specific for the transporter in primates. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25617245/ · DOI 10.1124/jpet.114.221523
trigger_kind
machinery_impairment Imported condition classification; unverified.
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 296–302
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Site-directed human transporter mutagenesis. · source_derived_draft · unverified_draft
## lithium-nact-variant A protein variant can change responsiveness independently of intake. F500W increased baseline transport but nearly eliminated additional lithium stimulation of human NaCT. Model: Site-directed human transporter mutagenesis. Limitations: Engineered variant, not evidence of a common human nutritional phenotype. Evidence access: Primary abstract Species-specific influence of lithium on the activity of SLC13A5 (NaCT): lithium-induced activation is specific for the transporter in primates. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25617245/ · DOI 10.1124/jpet.114.221523
Complete structured claim and evidence
LiCl stimulated glycogen synthesis from glucose in normal and diabetic-rat hepatocytes, with increased glycogen-synthase activity ratio.
Lithium ion (Li+) → Rat hepatocyte glycogen synthesis source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Rat hepatocytes; 20 mM glucose; concentration/time dependence.
limitations
Isolated cells, not a diabetes treatment trial.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
A carbohydrate-storage response depends on the available carbon source.
primary_references
Lithium restores glycogen synthesis from glucose in hepatocytes from diabetic rats. · 1993 · https://pubmed.ncbi.nlm.nih.gov/8460950/ · DOI 10.1006/abbi.1993.1164
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat hepatocytes; 20 mM glucose; concentration/time dependence. · source_derived_draft · unverified_draft
## lithium-glycogen-glucose A carbohydrate-storage response depends on the available carbon source. LiCl stimulated glycogen synthesis from glucose in normal and diabetic-rat hepatocytes, with increased glycogen-synthase activity ratio. Model: Rat hepatocytes; 20 mM glucose; concentration/time dependence. Limitations: Isolated cells, not a diabetes treatment trial. Evidence access: Primary abstract Lithium restores glycogen synthesis from glucose in hepatocytes from diabetic rats. · 1993 · https://pubmed.ncbi.nlm.nih.gov/8460950/ · DOI 10.1006/abbi.1993.1164
Complete structured claim and evidence
LiCl did not increase glycogen accumulation with lactate and pyruvate in the same hepatocyte study.
Lithium ion (Li+) → Rat hepatocyte glycogen synthesis source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Rat hepatocytes; simultaneous synthase and phosphorylase activation.
limitations
Context-dependent null result, not an unexplained contradiction.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Changing the starting substrate changed the outcome.
primary_references
Lithium restores glycogen synthesis from glucose in hepatocytes from diabetic rats. · 1993 · https://pubmed.ncbi.nlm.nih.gov/8460950/ · DOI 10.1006/abbi.1993.1164
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 312–318
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat hepatocytes; simultaneous synthase and phosphorylase activation. · source_derived_draft · unverified_draft
## lithium-glycogen-substrate-null Changing the starting substrate changed the outcome. LiCl did not increase glycogen accumulation with lactate and pyruvate in the same hepatocyte study. Model: Rat hepatocytes; simultaneous synthase and phosphorylase activation. Limitations: Context-dependent null result, not an unexplained contradiction. Evidence access: Primary abstract Lithium restores glycogen synthesis from glucose in hepatocytes from diabetic rats. · 1993 · https://pubmed.ncbi.nlm.nih.gov/8460950/ · DOI 10.1006/abbi.1993.1164
Complete structured claim and evidence
Collecting-duct Scnn1a deletion protected lithium-treated mice against polyuria and loss of urine concentration.
Mouse epithelial sodium-channel alpha / Scnn1a → Mouse urine-concentrating response during lithium exposure source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Collecting-duct-specific mouse knockout and chronic lithium treatment.
limitations
Protection supports ENaC-mediated entry; connecting-tubule expression remained intact.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
A sodium channel helps lithium reach vulnerable kidney cells.
primary_references
alphaENaC-mediated lithium absorption promotes nephrogenic diabetes insipidus. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21051735/ · DOI 10.1681/ASN.2010070734
trigger_kind
machinery_impairment Imported condition classification; unverified.
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 320–326
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Collecting-duct-specific mouse knockout and chronic lithium treatment. · source_derived_draft · unverified_draft
## lithium-enac-entry A sodium channel helps lithium reach vulnerable kidney cells. Collecting-duct Scnn1a deletion protected lithium-treated mice against polyuria and loss of urine concentration. Model: Collecting-duct-specific mouse knockout and chronic lithium treatment. Limitations: Protection supports ENaC-mediated entry; connecting-tubule expression remained intact. Evidence access: Primary abstract alphaENaC-mediated lithium absorption promotes nephrogenic diabetes insipidus. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21051735/ · DOI 10.1681/ASN.2010070734
Complete structured claim and evidence
Chronic lithium reduced AQP2 in cortex/outer medulla and inner medulla of control mice.
Lithium ion (Li+) → Mouse aquaporin 2 / Aqp2 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse collecting-duct study.
limitations
Residual inner-medullary reduction persisted in Scnn1a knockout; not every AQP2 change required this entry route.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Fewer water channels can reduce water recovery from urine.
primary_references
alphaENaC-mediated lithium absorption promotes nephrogenic diabetes insipidus. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21051735/ · DOI 10.1681/ASN.2010070734
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse collecting-duct study. · source_derived_draft · unverified_draft
## lithium-aqp2-down Fewer water channels can reduce water recovery from urine. Chronic lithium reduced AQP2 in cortex/outer medulla and inner medulla of control mice. Model: Mouse collecting-duct study. Limitations: Residual inner-medullary reduction persisted in Scnn1a knockout; not every AQP2 change required this entry route. Evidence access: Primary abstract alphaENaC-mediated lithium absorption promotes nephrogenic diabetes insipidus. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21051735/ · DOI 10.1681/ASN.2010070734
Complete structured claim and evidence
Urine-concentrating impairment and lower urinary AQP2/cAMP correlated with lithium-treatment duration in patients.
Lithium ion (Li+) → Human urine-concentrating response during lithium treatment source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
45 lithium-treated patients versus 42 on other psychotropics; desmopressin challenge.
limitations
Observational comparison cannot remove all confounding; urinary AQP2 is a marker, not a full tissue inventory.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Human kidney findings connect the cellular route to water balance.
primary_references
Lithium-induced nephrogenic diabetes insipidus: renal effects of amiloride. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18596116/ · DOI 10.2215/CJN.01640408
trigger_kind
biomarker_context Imported condition classification; unverified.
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 336–342
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 45 lithium-treated patients versus 42 on other psychotropics; desmopressin challenge. · source_derived_draft · unverified_draft
## lithium-human-concentration Human kidney findings connect the cellular route to water balance. Urine-concentrating impairment and lower urinary AQP2/cAMP correlated with lithium-treatment duration in patients. Model: 45 lithium-treated patients versus 42 on other psychotropics; desmopressin challenge. Limitations: Observational comparison cannot remove all confounding; urinary AQP2 is a marker, not a full tissue inventory. Evidence access: Primary abstract Lithium-induced nephrogenic diabetes insipidus: renal effects of amiloride. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18596116/ · DOI 10.2215/CJN.01640408
Complete structured claim and evidence
Amiloride increased maximal urine osmolality and AQP2 excretion in an eleven-patient crossover trial during lithium therapy.
Amiloride → Human urine-concentrating response during lithium treatment source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Randomized placebo-controlled crossover; six-week periods.
limitations
Small trial; reduced lithium entry was inferred, not directly measured in patient kidney cells.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Blocking a sodium channel improved the measured water response.
primary_references
Lithium-induced nephrogenic diabetes insipidus: renal effects of amiloride. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18596116/ · DOI 10.2215/CJN.01640408
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Randomized placebo-controlled crossover; six-week periods. · source_derived_draft · unverified_draft
## lithium-amiloride-human Blocking a sodium channel improved the measured water response. Amiloride increased maximal urine osmolality and AQP2 excretion in an eleven-patient crossover trial during lithium therapy. Model: Randomized placebo-controlled crossover; six-week periods. Limitations: Small trial; reduced lithium entry was inferred, not directly measured in patient kidney cells. Evidence access: Primary abstract Lithium-induced nephrogenic diabetes insipidus: renal effects of amiloride. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18596116/ · DOI 10.2215/CJN.01640408
Complete structured claim and evidence
Single 300- and 600-mg lithium-carbonate doses increased 24-hour sodium excretion by about 17 and 48 mmol, respectively.
Lithium carbonate → Human urinary sodium excretion source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
15 healthy volunteers; randomized blinded crossover and fixed sodium/potassium intake.
limitations
Salt doses describe the experiment, not dosing advice; a test dose can perturb a clearance measurement.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Lithium exposure can change sodium balance.
primary_references
Effect of a single test dose of lithium carbonate on sodium and potassium excretion in man. · 1991 · https://pubmed.ncbi.nlm.nih.gov/1649725/ · DOI 10.1042/cs0810059
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 15 healthy volunteers; randomized blinded crossover and fixed sodium/potassium intake. · source_derived_draft · unverified_draft
## lithium-sodium-excretion Lithium exposure can change sodium balance. Single 300- and 600-mg lithium-carbonate doses increased 24-hour sodium excretion by about 17 and 48 mmol, respectively. Model: 15 healthy volunteers; randomized blinded crossover and fixed sodium/potassium intake. Limitations: Salt doses describe the experiment, not dosing advice; a test dose can perturb a clearance measurement. Evidence access: Primary abstract Effect of a single test dose of lithium carbonate on sodium and potassium excretion in man. · 1991 · https://pubmed.ncbi.nlm.nih.gov/1649725/ · DOI 10.1042/cs0810059
Complete structured claim and evidence
Potassium excretion increased after 600 mg lithium carbonate but not after 300 mg in the volunteer study.
Lithium carbonate → Human urinary potassium excretion source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
15 healthy adults; about 19 mmol extra potassium over 24 hours at the higher dose.
limitations
Not evidence that every lithium user develops potassium depletion.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
The potassium response depended on exposure.
primary_references
Effect of a single test dose of lithium carbonate on sodium and potassium excretion in man. · 1991 · https://pubmed.ncbi.nlm.nih.gov/1649725/ · DOI 10.1042/cs0810059
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 360–366
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 15 healthy adults; about 19 mmol extra potassium over 24 hours at the higher dose. · source_derived_draft · unverified_draft
## lithium-potassium-excretion The potassium response depended on exposure. Potassium excretion increased after 600 mg lithium carbonate but not after 300 mg in the volunteer study. Model: 15 healthy adults; about 19 mmol extra potassium over 24 hours at the higher dose. Limitations: Not evidence that every lithium user develops potassium depletion. Evidence access: Primary abstract Effect of a single test dose of lithium carbonate on sodium and potassium excretion in man. · 1991 · https://pubmed.ncbi.nlm.nih.gov/1649725/ · DOI 10.1042/cs0810059
Complete structured claim and evidence
Indomethacin increased fractional lithium reabsorption on both high- and low-sodium diets in seven volunteers.
Indomethacin → Human renal lithium reabsorption source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
200 versus 40 mmol/day sodium; reabsorption 71 to 75% and 75 to 81%, respectively.
limitations
Not a recommendation to change salt intake; lithium clearance was not a universally pure proximal-tubule marker.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Sodium intake changes the setting for a drug interaction.
primary_references
Indomethacin increases renal lithium reabsorption in man. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2494594/
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 368–374
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 200 versus 40 mmol/day sodium; reabsorption 71 to 75% and 75 to 81%, respectively. · source_derived_draft · unverified_draft
## lithium-sodium-renal-context Sodium intake changes the setting for a drug interaction. Indomethacin increased fractional lithium reabsorption on both high- and low-sodium diets in seven volunteers. Model: 200 versus 40 mmol/day sodium; reabsorption 71 to 75% and 75 to 81%, respectively. Limitations: Not a recommendation to change salt intake; lithium clearance was not a universally pure proximal-tubule marker. Evidence access: Primary abstract Indomethacin increases renal lithium reabsorption in man. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2494594/
Complete structured claim and evidence
Indomethacin raised plasma lithium while lowering renal lithium clearance in seven studied people.
Indomethacin → Human serum lithium concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Three psychiatric patients and four volunteers; approximately 31% mean clearance reduction.
limitations
Small historical study; magnitude is not universal for all NSAIDs.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
A medicine can raise lithium exposure by slowing its removal.
primary_references
Indomethacin increases plasma lithium. · 1979 · https://pubmed.ncbi.nlm.nih.gov/444956/ · DOI 10.1136/bmj.1.6171.1115
trigger_kind
biomarker_context Imported condition classification; unverified.
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 376–382
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Three psychiatric patients and four volunteers; approximately 31% mean clearance reduction. · source_derived_draft · unverified_draft
## lithium-nsaid-clearance A medicine can raise lithium exposure by slowing its removal. Indomethacin raised plasma lithium while lowering renal lithium clearance in seven studied people. Model: Three psychiatric patients and four volunteers; approximately 31% mean clearance reduction. Limitations: Small historical study; magnitude is not universal for all NSAIDs. Evidence access: Primary abstract Indomethacin increases plasma lithium. · 1979 · https://pubmed.ncbi.nlm.nih.gov/444956/ · DOI 10.1136/bmj.1.6171.1115
Complete structured claim and evidence
Chronic lithium-treated patients required a higher calcium level for comparable PTH suppression during calcium/citrate infusions.
Lithium ion (Li+) → Human calcium–PTH suppression set-point source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Seven lithium-treated women versus seven controls; mean set-point 5.08 versus 4.88 mg/dL ionized calcium.
limitations
Supports altered feedback, not direct lithium binding to human CaSR.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Calcium feedback to the parathyroid gland was reset.
primary_references
Alterations in parathyroid dynamics in lithium-treated subjects. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9284708/ · DOI 10.1210/jcem.82.9.4218
trigger_kind
biomarker_context Imported condition classification; unverified.
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 384–390
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Seven lithium-treated women versus seven controls; mean set-point 5.08 versus 4.88 mg/dL ionized calcium. · source_derived_draft · unverified_draft
## lithium-pth-setpoint Calcium feedback to the parathyroid gland was reset. Chronic lithium-treated patients required a higher calcium level for comparable PTH suppression during calcium/citrate infusions. Model: Seven lithium-treated women versus seven controls; mean set-point 5.08 versus 4.88 mg/dL ionized calcium. Limitations: Supports altered feedback, not direct lithium binding to human CaSR. Evidence access: Primary abstract Alterations in parathyroid dynamics in lithium-treated subjects. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9284708/ · DOI 10.1210/jcem.82.9.4218
Complete structured claim and evidence
Lithium reduced hormonal and nonhormonal thyroid iodine release in human radioiodine kinetic studies.
Lithium ion (Li+) → Human thyroid hormonal and nonhormonal iodine release source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Eight kinetic studies in seven thyrotoxic women; serum lithium about 1 mEq/L.
limitations
Compartment-model inference; not evidence that lithium simply removes iodine from the body.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Making thyroid hormone and releasing it are separate steps.
primary_references
The use of lithium in the treatment of thyrotoxicosis. · 1972 · https://pubmed.ncbi.nlm.nih.gov/4115707/ · DOI 10.1172/JCI107094
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 392–398
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Eight kinetic studies in seven thyrotoxic women; serum lithium about 1 mEq/L. · source_derived_draft · unverified_draft
## lithium-thyroid-release Making thyroid hormone and releasing it are separate steps. Lithium reduced hormonal and nonhormonal thyroid iodine release in human radioiodine kinetic studies. Model: Eight kinetic studies in seven thyrotoxic women; serum lithium about 1 mEq/L. Limitations: Compartment-model inference; not evidence that lithium simply removes iodine from the body. Evidence access: Primary abstract The use of lithium in the treatment of thyrotoxicosis. · 1972 · https://pubmed.ncbi.nlm.nih.gov/4115707/ · DOI 10.1172/JCI107094
Complete structured claim and evidence
Five kinetic studies also required slower serum hormone disappearance to fit lithium-associated observations.
Lithium ion (Li+) → Human serum thyroid-hormone disappearance rate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human radioiodine compartment modeling.
limitations
Not demonstrated inhibition of a particular deiodinase; do not infer selenium depletion.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Blood hormone concentration reflects both release and removal.
primary_references
The use of lithium in the treatment of thyrotoxicosis. · 1972 · https://pubmed.ncbi.nlm.nih.gov/4115707/ · DOI 10.1172/JCI107094
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 400–406
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human radioiodine compartment modeling. · source_derived_draft · unverified_draft
## lithium-thyroid-turnover Blood hormone concentration reflects both release and removal. Five kinetic studies also required slower serum hormone disappearance to fit lithium-associated observations. Model: Human radioiodine compartment modeling. Limitations: Not demonstrated inhibition of a particular deiodinase; do not infer selenium depletion. Evidence access: Primary abstract The use of lithium in the treatment of thyrotoxicosis. · 1972 · https://pubmed.ncbi.nlm.nih.gov/4115707/ · DOI 10.1172/JCI107094
Complete structured claim and evidence
LiCl inhibited GSK3beta and stabilized free beta-catenin in cultured human thyrocytes.
Lithium ion (Li+) → Human beta-catenin / CTNNB1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Primary and neoplastic human-cell preparations; dose-response assays.
limitations
Historical cell-line identities and experimental conditions limit extrapolation.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Thyroid growth signaling can change independently of hormone release.
primary_references
Lithium stimulates proliferation in cultured thyrocytes by activating Wnt/beta-catenin signalling. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16322400/ · DOI 10.1530/eje.1.02038
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary and neoplastic human-cell preparations; dose-response assays. · source_derived_draft · unverified_draft
## lithium-thyroid-beta-catenin Thyroid growth signaling can change independently of hormone release. LiCl inhibited GSK3beta and stabilized free beta-catenin in cultured human thyrocytes. Model: Primary and neoplastic human-cell preparations; dose-response assays. Limitations: Historical cell-line identities and experimental conditions limit extrapolation. Evidence access: Primary abstract Lithium stimulates proliferation in cultured thyrocytes by activating Wnt/beta-catenin signalling. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16322400/ · DOI 10.1530/eje.1.02038
Complete structured claim and evidence
At 5 mM LiCl, thyrocyte proliferation increased; dominant-negative TCF4 reduced this response by about half.
Lithium ion (Li+) → Human cultured-thyrocyte proliferation source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human cultured thyrocytes; TCF4 versus CREB pathway perturbation.
limitations
High cell-culture exposure; not a quantified human goiter or cancer risk.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Blocking a downstream regulator weakened the growth response.
primary_references
Lithium stimulates proliferation in cultured thyrocytes by activating Wnt/beta-catenin signalling. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16322400/ · DOI 10.1530/eje.1.02038
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 416–422
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cultured thyrocytes; TCF4 versus CREB pathway perturbation. · source_derived_draft · unverified_draft
## lithium-thyroid-wnt-growth Blocking a downstream regulator weakened the growth response. At 5 mM LiCl, thyrocyte proliferation increased; dominant-negative TCF4 reduced this response by about half. Model: Human cultured thyrocytes; TCF4 versus CREB pathway perturbation. Limitations: High cell-culture exposure; not a quantified human goiter or cancer risk. Evidence access: Primary abstract Lithium stimulates proliferation in cultured thyrocytes by activating Wnt/beta-catenin signalling. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16322400/ · DOI 10.1530/eje.1.02038
Complete structured claim and evidence
Human brain analyses found lithium enrichment in amyloid plaques and lower non-plaque lithium associated with cognition.
Human AD/MCI amyloid-plaque compartment → Human non-plaque cortical lithium measurement source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human postmortem cohorts; elemental mapping and fractionation.
limitations
Association cannot establish the direction of disease causation or a clinical diagnostic threshold.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Where lithium is located may matter more than a total measurement.
primary_references
Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x
trigger_kind
biomarker_context Imported condition classification; unverified.
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 424–430
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human postmortem cohorts; elemental mapping and fractionation. · source_derived_draft · unverified_draft
## lithium-human-brain-association Where lithium is located may matter more than a total measurement. Human brain analyses found lithium enrichment in amyloid plaques and lower non-plaque lithium associated with cognition. Model: Human postmortem cohorts; elemental mapping and fractionation. Limitations: Association cannot establish the direction of disease causation or a clinical diagnostic threshold. Evidence access: Primary full text Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x
Complete structured claim and evidence
Dietary lithium depletion reduced endogenous cortical lithium by about half in the mouse experiments.
Experimental mouse low-lithium diet → Mouse cortical lithium availability source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Wild-type and transgenic AD mouse paradigms; regimen-specific effects.
limitations
Animal depletion does not define a human requirement or safe supplement dose.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
The study experimentally lowered the brain pool.
primary_references
Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 432–438
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Wild-type and transgenic AD mouse paradigms; regimen-specific effects. · source_derived_draft · unverified_draft
## lithium-dietary-depletion The study experimentally lowered the brain pool. Dietary lithium depletion reduced endogenous cortical lithium by about half in the mouse experiments. Model: Wild-type and transgenic AD mouse paradigms; regimen-specific effects. Limitations: Animal depletion does not define a human requirement or safe supplement dose. Evidence access: Primary full text Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x
Complete structured claim and evidence
Lithium depletion increased amyloid deposition in AD-model mice.
Mouse cortical lithium availability → Mouse AD-model amyloid burden source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
3xTg and J20 mice on low-lithium diets.
limitations
Same study as the other depletion records, not independent replications.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Lower availability worsened an experimentally measured pathology.
primary_references
Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 440–446
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 3xTg and J20 mice on low-lithium diets. · source_derived_draft · unverified_draft
## lithium-depletion-amyloid Lower availability worsened an experimentally measured pathology. Lithium depletion increased amyloid deposition in AD-model mice. Model: 3xTg and J20 mice on low-lithium diets. Limitations: Same study as the other depletion records, not independent replications. Evidence access: Primary full text Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x
Complete structured claim and evidence
Lithium depletion increased phosphorylated tau in 3xTg mice.
Mouse cortical lithium availability → Mouse AD-model tau phosphorylation source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Dietary-depletion experiment; hippocampal phospho-tau measurements.
limitations
Transgenic mouse result; not proof of human causation.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
A second pathological protein response changed.
primary_references
Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 448–454
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Dietary-depletion experiment; hippocampal phospho-tau measurements. · source_derived_draft · unverified_draft
## lithium-depletion-tau A second pathological protein response changed. Lithium depletion increased phosphorylated tau in 3xTg mice. Model: Dietary-depletion experiment; hippocampal phospho-tau measurements. Limitations: Transgenic mouse result; not proof of human causation. Evidence access: Primary full text Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x
Complete structured claim and evidence
Lithium depletion increased GSK3beta expression and activation-associated signals in mouse brain.
Mouse cortical lithium availability → Mouse glycogen synthase kinase 3 beta / Gsk3b source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Mouse neurons, oligodendrocytes and microglial analyses.
limitations
Not a universal linear relation between serum lithium and enzyme activity.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
The enzyme connects availability to downstream responses.
primary_references
Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 456–462
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse neurons, oligodendrocytes and microglial analyses. · source_derived_draft · unverified_draft
## lithium-depletion-gsk3 The enzyme connects availability to downstream responses. Lithium depletion increased GSK3beta expression and activation-associated signals in mouse brain. Model: Mouse neurons, oligodendrocytes and microglial analyses. Limitations: Not a universal linear relation between serum lithium and enzyme activity. Evidence access: Primary full text Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x
Complete structured claim and evidence
Microglia from lithium-depleted mice showed impaired amyloid uptake and degradation.
Mouse cortical lithium availability → Mouse microglial amyloid uptake and degradation source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Primary microglia from dietary-depletion experiments.
limitations
Cell isolation and model context retained; not a human immune-treatment result.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Brain immune cells became less effective at clearing amyloid.
primary_references
Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 464–470
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary microglia from dietary-depletion experiments. · source_derived_draft · unverified_draft
## lithium-depletion-microglia Brain immune cells became less effective at clearing amyloid. Microglia from lithium-depleted mice showed impaired amyloid uptake and degradation. Model: Primary microglia from dietary-depletion experiments. Limitations: Cell isolation and model context retained; not a human immune-treatment result. Evidence access: Primary full text Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x
Complete structured claim and evidence
Lithium-depleted mice showed loss of oligodendrocytes and myelin-associated signals.
Mouse cortical lithium availability → Mouse brain myelin integrity source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Mouse dietary-depletion, histological and molecular comparisons.
limitations
Not a demonstrated human demyelinating disease mechanism or a substitute for established nutrient-deficiency diagnoses.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
The cells and insulation around nerve fibers were affected.
primary_references
Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 472–478
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse dietary-depletion, histological and molecular comparisons. · source_derived_draft · unverified_draft
## lithium-depletion-myelin The cells and insulation around nerve fibers were affected. Lithium-depleted mice showed loss of oligodendrocytes and myelin-associated signals. Model: Mouse dietary-depletion, histological and molecular comparisons. Limitations: Not a demonstrated human demyelinating disease mechanism or a substitute for established nutrient-deficiency diagnoses. Evidence access: Primary full text Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x
Complete structured claim and evidence
Dietary lithium depletion reduced synaptic markers and synapse density in the studied mice.
Mouse cortical lithium availability → Mouse synaptic integrity in lithium-depletion experiments source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Mouse brain imaging, protein and structural comparisons.
limitations
Same experimental program as the other depletion records; requires independent replication.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Connections between nerve cells also changed.
primary_references
Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 480–486
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse brain imaging, protein and structural comparisons. · source_derived_draft · unverified_draft
## lithium-depletion-synapses Connections between nerve cells also changed. Dietary lithium depletion reduced synaptic markers and synapse density in the studied mice. Model: Mouse brain imaging, protein and structural comparisons. Limitations: Same experimental program as the other depletion records; requires independent replication. Evidence access: Primary full text Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x
Complete structured claim and evidence
GSK3 inhibition restored amyloid uptake/degradation in microglia from lithium-depleted mice.
CHIR99021 → Mouse microglial amyloid uptake and degradation source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
CHIR99021 and companion PF-04802367 rescue assays.
limitations
Inhibitor rescue supports partial mediation, not a single-target explanation.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Blocking the downstream enzyme helped test the proposed chain.
primary_references
Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 488–494
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · CHIR99021 and companion PF-04802367 rescue assays. · source_derived_draft · unverified_draft
## lithium-gsk3-rescue Blocking the downstream enzyme helped test the proposed chain. GSK3 inhibition restored amyloid uptake/degradation in microglia from lithium-depleted mice. Model: CHIR99021 and companion PF-04802367 rescue assays. Limitations: Inhibitor rescue supports partial mediation, not a single-target explanation. Evidence access: Primary full text Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x
Complete structured claim and evidence
Endogenous lithium depletion did not change brain inositol in the reported mouse comparison.
Mouse cortical lithium availability → Myo-inositol source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Mouse brain comparison with pharmacological IMPase rationale.
limitations
A scoped null measurement, not proof that inositol is irrelevant in every lithium setting.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Trace depletion did not reproduce every pharmacological pathway.
primary_references
Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 496–502
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse brain comparison with pharmacological IMPase rationale. · source_derived_draft · unverified_draft
## lithium-depletion-inositol-null Trace depletion did not reproduce every pharmacological pathway. Endogenous lithium depletion did not change brain inositol in the reported mouse comparison. Model: Mouse brain comparison with pharmacological IMPase rationale. Limitations: A scoped null measurement, not proof that inositol is irrelevant in every lithium setting. Evidence access: Primary full text Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x
Complete structured claim and evidence
Lithium orotate showed lower amyloid binding than carbonate in the study’s equilibrium-dialysis assays.
Lithium orotate → Lithium carbonate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Synthetic human Aβ42 oligomers/fibrils and controlled salt solutions.
limitations
Does not establish superior human brain delivery or product safety.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
The salt preparation changed measured binding.
primary_references
Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 504–510
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Synthetic human Aβ42 oligomers/fibrils and controlled salt solutions. · source_derived_draft · unverified_draft
## lithium-orotate-binding The salt preparation changed measured binding. Lithium orotate showed lower amyloid binding than carbonate in the study’s equilibrium-dialysis assays. Model: Synthetic human Aβ42 oligomers/fibrils and controlled salt solutions. Limitations: Does not establish superior human brain delivery or product safety. Evidence access: Primary full text Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x
Complete structured claim and evidence
Low-dose lithium orotate reduced amyloid pathology in the studied AD mouse models.
Lithium orotate → Mouse AD-model amyloid burden source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
3xTg and J20 mouse regimens; matched carbonate and sodium-orotate comparisons.
limitations
Experimental drinking-water concentration is not a human dose; no human orotate trial is established here.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Replacement improved a model outcome.
primary_references
Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 512–518
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 3xTg and J20 mouse regimens; matched carbonate and sodium-orotate comparisons. · source_derived_draft · unverified_draft
## lithium-orotate-model-pathology Replacement improved a model outcome. Low-dose lithium orotate reduced amyloid pathology in the studied AD mouse models. Model: 3xTg and J20 mouse regimens; matched carbonate and sodium-orotate comparisons. Limitations: Experimental drinking-water concentration is not a human dose; no human orotate trial is established here. Evidence access: Primary full text Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x
Complete structured claim and evidence
Lithium orotate improved memory measures in AD-model and ageing wild-type mice.
Lithium orotate → Mouse memory performance in lithium-depletion/replacement experiments source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Mouse behavioral assays with locomotor/visual control comparisons.
limitations
Not evidence of proven human dementia prevention.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Behavioral outcomes accompanied the molecular findings.
primary_references
Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 520–526
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse behavioral assays with locomotor/visual control comparisons. · source_derived_draft · unverified_draft
## lithium-orotate-model-memory Behavioral outcomes accompanied the molecular findings. Lithium orotate improved memory measures in AD-model and ageing wild-type mice. Model: Mouse behavioral assays with locomotor/visual control comparisons. Limitations: Not evidence of proven human dementia prevention. Evidence access: Primary full text Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x
Complete structured claim and evidence
A 61-person trial reported cognitive/functional stability with lithium versus decline with placebo over two years.
Lithium carbonate → Human MCI cognitive/functional outcomes during lithium trials source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Amnestic MCI; lithium carbonate target 0.25–0.5 mEq/L; NCT01055392.
limitations
Single trial; population, exposure, endpoints and follow-up differ from later studies.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
One small human trial reported a favorable result.
primary_references
Clinical and biological effects of long-term lithium treatment in older adults with amnestic mild cognitive impairment: randomised clinical trial. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30947755/ · DOI 10.1192/bjp.2019.76
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 528–534
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Amnestic MCI; lithium carbonate target 0.25–0.5 mEq/L; NCT01055392. · source_derived_draft · unverified_draft
## lithium-mci-positive One small human trial reported a favorable result. A 61-person trial reported cognitive/functional stability with lithium versus decline with placebo over two years. Model: Amnestic MCI; lithium carbonate target 0.25–0.5 mEq/L; NCT01055392. Limitations: Single trial; population, exposure, endpoints and follow-up differ from later studies. Evidence access: Primary abstract Clinical and biological effects of long-term lithium treatment in older adults with amnestic mild cognitive impairment: randomised clinical trial. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30947755/ · DOI 10.1192/bjp.2019.76
Complete structured claim and evidence
None of six coprimary outcomes met the prespecified significance threshold in the 2026 low-dose lithium trial.
Lithium carbonate → Human MCI cognitive/functional outcomes during lithium trials source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
NCT03185208; 83 randomized, 80 started; two years; prespecified P<.01.
limitations
Verbal-recall difference P=.05 and exploratory amyloid subgroups are not positive primary results.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
The newer pilot did not confirm its primary efficacy hypotheses.
primary_references
Low-Dose Lithium for Mild Cognitive Impairment: A Pilot Randomized Clinical Trial. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41770546/ · DOI 10.1001/jamaneurol.2026.0072
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 536–542
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · NCT03185208; 83 randomized, 80 started; two years; prespecified P<.01. · source_derived_draft · unverified_draft
## lithium-mci-2026-primary-null The newer pilot did not confirm its primary efficacy hypotheses. None of six coprimary outcomes met the prespecified significance threshold in the 2026 low-dose lithium trial. Model: NCT03185208; 83 randomized, 80 started; two years; prespecified P<.01. Limitations: Verbal-recall difference P=.05 and exploratory amyloid subgroups are not positive primary results. Evidence access: Primary full text Low-Dose Lithium for Mild Cognitive Impairment: A Pilot Randomized Clinical Trial. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41770546/ · DOI 10.1001/jamaneurol.2026.0072
Complete structured claim and evidence
Completers in the 2026 trial had mean serum lithium 0.17 mEq/L, with substantial variability.
Lithium carbonate → Human serum lithium concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Mean daily carbonate dose 195 mg; serum SD 0.13 mEq/L among completers.
limitations
Completer exposure is not the whole randomized population or a recommended target.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
The actual exposure matters when comparing trials.
primary_references
Low-Dose Lithium for Mild Cognitive Impairment: A Pilot Randomized Clinical Trial. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41770546/ · DOI 10.1001/jamaneurol.2026.0072
trigger_kind
biomarker_context Imported condition classification; unverified.
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 544–550
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mean daily carbonate dose 195 mg; serum SD 0.13 mEq/L among completers. · source_derived_draft · unverified_draft
## lithium-mci-2026-exposure The actual exposure matters when comparing trials. Completers in the 2026 trial had mean serum lithium 0.17 mEq/L, with substantial variability. Model: Mean daily carbonate dose 195 mg; serum SD 0.13 mEq/L among completers. Limitations: Completer exposure is not the whole randomized population or a recommended target. Evidence access: Primary full text Low-Dose Lithium for Mild Cognitive Impairment: A Pilot Randomized Clinical Trial. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41770546/ · DOI 10.1001/jamaneurol.2026.0072
Complete structured claim and evidence
A 71-person ten-week AD trial found no treatment effect on CSF biomarkers or lymphocyte GSK3 activity.
Lithium carbonate → Human AD trial CSF tau and lymphocyte GSK3 outcomes source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mild AD; six-week titration; serum target 0.5–0.8 mmol/L.
limitations
Short duration and different disease stage; neither proves lifelong efficacy nor rules out every regimen.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
A cell mechanism did not translate into measured target effects in this trial.
primary_references
Lithium trial in Alzheimer's disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19573486/
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 552–558
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mild AD; six-week titration; serum target 0.5–0.8 mmol/L. · source_derived_draft · unverified_draft
## lithium-ad-short-null A cell mechanism did not translate into measured target effects in this trial. A 71-person ten-week AD trial found no treatment effect on CSF biomarkers or lymphocyte GSK3 activity. Model: Mild AD; six-week titration; serum target 0.5–0.8 mmol/L. Limitations: Short duration and different disease stage; neither proves lifelong efficacy nor rules out every regimen. Evidence access: Primary abstract Lithium trial in Alzheimer's disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19573486/
Complete structured claim and evidence
Lithium monotherapy had fewer new mood-episode interventions than valproate in BALANCE; adding valproate was not clearly superior to lithium alone.
Lithium carbonate → New mood-episode intervention in the BALANCE trial source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
330 randomized bipolar-I patients; open-label treatment with masked event review; up to two years.
limitations
Combination run-in and open-label design matter; the trial does not identify a single molecular mediator.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Clinical mood efficacy has its own evidence, separate from dementia hypotheses.
primary_references
Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE): a randomised open-label trial. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20092882/ · DOI 10.1016/S0140-6736(09)61828-6
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 560–566
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 330 randomized bipolar-I patients; open-label treatment with masked event review; up to two years. · source_derived_draft · unverified_draft
## lithium-bipolar-relapse Clinical mood efficacy has its own evidence, separate from dementia hypotheses. Lithium monotherapy had fewer new mood-episode interventions than valproate in BALANCE; adding valproate was not clearly superior to lithium alone. Model: 330 randomized bipolar-I patients; open-label treatment with masked event review; up to two years. Limitations: Combination run-in and open-label design matter; the trial does not identify a single molecular mediator. Evidence access: Primary abstract Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE): a randomised open-label trial. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20092882/ · DOI 10.1016/S0140-6736(09)61828-6
Complete structured claim and evidence
Dehydration can promote lithium retention and toxicity.
Human volume depletion/dehydration → Human serum lithium concentration source_derived_draftungraded
Experimental context and source evidence
evidence_access
Official prescribing information
experimental_model
Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06.
limitations
Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Fluid loss can amplify exposure.
primary_references
Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 568–574
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. · source_derived_draft · unverified_draft
## lithium-dehydration Fluid loss can amplify exposure. Dehydration can promote lithium retention and toxicity. Model: Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. Limitations: Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows. Evidence access: Official prescribing information Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada
Complete structured claim and evidence
Diuretic-associated sodium loss can reduce lithium clearance.
Diuretic-induced sodium loss → Lithium ion (Li+) source_derived_draftungraded
Experimental context and source evidence
evidence_access
Official prescribing information
experimental_model
Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06.
limitations
Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Sodium loss can slow lithium removal.
primary_references
Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 576–582
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. · source_derived_draft · unverified_draft
## lithium-diuretic-sodium Sodium loss can slow lithium removal. Diuretic-associated sodium loss can reduce lithium clearance. Model: Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. Limitations: Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows. Evidence access: Official prescribing information Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada
Complete structured claim and evidence
Renin–angiotensin-system antagonists can increase steady-state lithium concentrations.
Renin–angiotensin-system antagonist exposure → Human serum lithium concentration source_derived_draftungraded
Experimental context and source evidence
evidence_access
Official prescribing information
experimental_model
Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06.
limitations
Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Blood-pressure medicines can change exposure.
primary_references
Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 584–590
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. · source_derived_draft · unverified_draft
## lithium-ras-interaction Blood-pressure medicines can change exposure. Renin–angiotensin-system antagonists can increase steady-state lithium concentrations. Model: Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. Limitations: Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows. Evidence access: Official prescribing information Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada
Complete structured claim and evidence
SGLT2 inhibitors may lower serum lithium.
SGLT2 inhibitor exposure → Human serum lithium concentration source_derived_draftungraded
Experimental context and source evidence
evidence_access
Official prescribing information
experimental_model
Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06.
limitations
Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Not all renal drug interactions increase exposure.
primary_references
Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 592–598
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. · source_derived_draft · unverified_draft
## lithium-sglt2-interaction Not all renal drug interactions increase exposure. SGLT2 inhibitors may lower serum lithium. Model: Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. Limitations: Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows. Evidence access: Official prescribing information Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada
Complete structured claim and evidence
Serotonergic co-medication can increase serotonin-syndrome risk with lithium.
Concurrent serotonergic-drug exposure → Serotonin-syndrome risk during lithium coexposure source_derived_draftungraded
Experimental context and source evidence
evidence_access
Official prescribing information
experimental_model
Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06.
limitations
Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
A signaling interaction differs from a clearance interaction.
primary_references
Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 600–606
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. · source_derived_draft · unverified_draft
## lithium-serotonergic-interaction A signaling interaction differs from a clearance interaction. Serotonergic co-medication can increase serotonin-syndrome risk with lithium. Model: Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. Limitations: Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows. Evidence access: Official prescribing information Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada
Complete structured claim and evidence
Lithium is not metabolized and is eliminated primarily through the kidneys.
Lithium ion (Li+) → Human renal lithium elimination source_derived_draftungraded
Experimental context and source evidence
evidence_access
Official prescribing information
experimental_model
Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06.
limitations
Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Kidney handling controls removal.
primary_references
Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 608–614
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. · source_derived_draft · unverified_draft
## lithium-renal-elimination Kidney handling controls removal. Lithium is not metabolized and is eliminated primarily through the kidneys. Model: Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. Limitations: Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows. Evidence access: Official prescribing information Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada
Complete structured claim and evidence
Xanthine preparations can increase urinary lithium excretion and lower serum levels.
Xanthine-preparation exposure → Lithium ion (Li+) source_derived_draftungraded
Experimental context and source evidence
evidence_access
Official prescribing information
experimental_model
Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06.
limitations
Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows.
nutrient_topic
Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium
plain_language
Another compound class can change renal handling.
primary_references
Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada
Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 616–622
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. · source_derived_draft · unverified_draft
## lithium-xanthine-excretion Another compound class can change renal handling. Xanthine preparations can increase urinary lithium excretion and lower serum levels. Model: Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. Limitations: Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows. Evidence access: Official prescribing information Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada
Complete structured claim and evidence
The label warns that lithium or antithyroid drugs can add to hypothyroid and goitrogenic effects.
Potassium iodide → Goitrous hypothyroidism source_derived_draftungraded
Experimental context and source evidence
experimental_model
2025 SSKI manufacturer label; 1 g KI/mL formulation.
exposure_category
Study-specific exposure, including pharmacological and in-vitro conditions; normal is the schema fallback outside the three availability categories.
limitations
Label warning, not a quantified primary interaction trial; applicability depends on exposure and patient context.
nutrient_topic
Potassium iodide research collection; shared-anion and comparator studies are not all KI interventions. · Potassium iodide
plain_language
Different drugs can converge on reduced thyroid function.
primary_references
SSKI product label, July 2025 · manufacturer label; DailyMed lists UNAPPROVED DRUG OTHER; not a trial or FDA approval · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ca1d3449-ea29-49a4-8863-365ec95f1553
Potassium iodide: thyroid and non-thyroid mechanisms, interactions and discovery questions (2026-09-18) · lines 456–462
AI-assisted research curation; primary-study references, chemical references and label statements individually identified. Not publisher full text. · supports · 2025 SSKI manufacturer label; 1 g KI/mL formulation. · source_derived_draft · unverified_draft
## ki-lithium Different drugs can converge on reduced thyroid function. The label warns that lithium or antithyroid drugs can add to hypothyroid and goitrogenic effects. Model: 2025 SSKI manufacturer label; 1 g KI/mL formulation. Limitations: Label warning, not a quantified primary interaction trial; applicability depends on exposure and patient context. Evidence location: Primary abstract SSKI product label, July 2025 · manufacturer label; DailyMed lists UNAPPROVED DRUG OTHER; not a trial or FDA approval · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ca1d3449-ea29-49a4-8863-365ec95f1553
Complete structured claim and evidence
Vasopressin increased apical AQP2 labeling and shifted AQP2 from intracellular vesicles toward the apical membrane.
Arginine vasopressin / antidiuretic hormone → Apical collecting-duct aquaporin-2 abundance source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/sodium-research/7532304.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "11ee4ffb0794466d6aaf66a0490324f1669a6082a647e8b185f7c5c47eec92c4", "start_char": 0, "end_char": 1588, "text_sha256": "11ee4ffb0794466d6aaf66a0490324f1669a6082a647e8b185f7c5c47eec92c4"}
experimental_model
Perfused collecting ducts with matched water-permeability measurement and immunoelectron microscopy
exposure
Vasopressin addition and withdrawal
limitations
Direct water-channel trafficking experiment; no claim that sodium dietary deficiency caused the response.
nutrient_topic
Sodium research collection; topical membership is not evidence of a direct dietary effect. · Sodium
organism
Rat
plain_language
The kidney can retain more water by moving water channels to the cell surface.
primary_references
[sodium-p7532304] Vasopressin increases water permeability of kidney collecting duct by inducing translocation of aquaporin-CD water channels to plasma membrane. (1995). https://pubmed.ncbi.nlm.nih.gov/7532304/ DOI: 10.1073/pnas.92.4.1013
tissue_or_cell_type
Inner medullary collecting duct
Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 421–432
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Perfused collecting ducts with matched water-permeability measurement and immunoelectron microscopy · source_derived_draft · unverified_draft
### sodium-avp-aqp2 Vasopressin increased apical AQP2 labeling and shifted AQP2 from intracellular vesicles toward the apical membrane. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The kidney can retain more water by moving water channels to the cell surface. organism: Rat tissue_or_cell_type: Inner medullary collecting duct experimental_model: Perfused collecting ducts with matched water-permeability measurement and immunoelectron microscopy limitations: Direct water-channel trafficking experiment; no claim that sodium dietary deficiency caused the response. exposure: Vasopressin addition and withdrawal evidence_span: {"source_cache": "artifacts/sodium-research/7532304.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "11ee4ffb0794466d6aaf66a0490324f1669a6082a647e8b185f7c5c47eec92c4", "start_char": 0, "end_char": 1588, "text_sha256": "11ee4ffb0794466d6aaf66a0490324f1669a6082a647e8b185f7c5c47eec92c4"} [sodium-p7532304] Vasopressin increases water permeability of kidney collecting duct by inducing translocation of aquaporin-CD water channels to plasma membrane. (1995). https://pubmed.ncbi.nlm.nih.gov/7532304/ DOI: 10.1073/pnas.92.4.1013
Complete structured claim and evidence
Water permeability rose during vasopressin exposure and fell after withdrawal in parallel with AQP2 redistribution.
Arginine vasopressin / antidiuretic hormone → Collecting-duct osmotic water permeability source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/sodium-research/7532304.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "11ee4ffb0794466d6aaf66a0490324f1669a6082a647e8b185f7c5c47eec92c4", "start_char": 0, "end_char": 1588, "text_sha256": "11ee4ffb0794466d6aaf66a0490324f1669a6082a647e8b185f7c5c47eec92c4"}
experimental_model
Perfused collecting ducts with matched water-permeability measurement and immunoelectron microscopy
exposure
Vasopressin addition and withdrawal
limitations
Direct water-channel trafficking experiment; no claim that sodium dietary deficiency caused the response.
nutrient_topic
Sodium research collection; topical membership is not evidence of a direct dietary effect. · Sodium
organism
Rat
plain_language
This is a water-control mechanism that must be considered when interpreting blood sodium.
primary_references
[sodium-p7532304] Vasopressin increases water permeability of kidney collecting duct by inducing translocation of aquaporin-CD water channels to plasma membrane. (1995). https://pubmed.ncbi.nlm.nih.gov/7532304/ DOI: 10.1073/pnas.92.4.1013
tissue_or_cell_type
Inner medullary collecting duct
Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 434–445
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Perfused collecting ducts with matched water-permeability measurement and immunoelectron microscopy · source_derived_draft · unverified_draft
### sodium-avp-water Water permeability rose during vasopressin exposure and fell after withdrawal in parallel with AQP2 redistribution. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: This is a water-control mechanism that must be considered when interpreting blood sodium. organism: Rat tissue_or_cell_type: Inner medullary collecting duct experimental_model: Perfused collecting ducts with matched water-permeability measurement and immunoelectron microscopy limitations: Direct water-channel trafficking experiment; no claim that sodium dietary deficiency caused the response. exposure: Vasopressin addition and withdrawal evidence_span: {"source_cache": "artifacts/sodium-research/7532304.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "11ee4ffb0794466d6aaf66a0490324f1669a6082a647e8b185f7c5c47eec92c4", "start_char": 0, "end_char": 1588, "text_sha256": "11ee4ffb0794466d6aaf66a0490324f1669a6082a647e8b185f7c5c47eec92c4"} [sodium-p7532304] Vasopressin increases water permeability of kidney collecting duct by inducing translocation of aquaporin-CD water channels to plasma membrane. (1995). https://pubmed.ncbi.nlm.nih.gov/7532304/ DOI: 10.1073/pnas.92.4.1013
Complete structured claim and evidence
IMPA1-deficient patient-derived neuronal progenitors showed impaired proliferation, cell-cycle arrest, apoptosis and reduced neuronal differentiation.
IMPA1 (human inositol monophosphatase 1) → Neural progenitor survival and neurogenesis source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/inositol-research/32839513.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ca10517672cac78ad8cdb0c593f14f73f1989e55977432d979690eebc3eefed", "start_char": 0, "end_char": 1711, "text_sha256": "5ca10517672cac78ad8cdb0c593f14f73f1989e55977432d979690eebc3eefed"}
experimental_model
Patient-derived iPSC differentiation and rescue
exposure
Biallelic IMPA1 defect and myo-inositol-supplemented medium
limitations
Cellular rescue is not demonstrated neurological benefit in treated patients; effects were lineage-specific.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
Failure of the inositol-processing machinery affected developing nerve cells.
primary_references
[ino-p32839513] Inositol monophosphatase 1 (IMPA1) mutation in intellectual disability patients impairs neurogenesis but not gliogenesis. (2021). https://pubmed.ncbi.nlm.nih.gov/32839513/ DOI: 10.1038/s41380-020-00862-9
tissue_or_cell_type
Hippocampal dentate-gyrus-like neuronal progenitors
trigger_kind
machinery_impairment Imported condition classification; unverified.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1263–1274
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient-derived iPSC differentiation and rescue · source_derived_draft · unverified_draft
### ino-impa1-progenitors IMPA1-deficient patient-derived neuronal progenitors showed impaired proliferation, cell-cycle arrest, apoptosis and reduced neuronal differentiation. Condition category: machinery_impairment nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Failure of the inositol-processing machinery affected developing nerve cells. organism: Homo sapiens tissue_or_cell_type: Hippocampal dentate-gyrus-like neuronal progenitors experimental_model: Patient-derived iPSC differentiation and rescue limitations: Cellular rescue is not demonstrated neurological benefit in treated patients; effects were lineage-specific. exposure: Biallelic IMPA1 defect and myo-inositol-supplemented medium evidence_span: {"source_cache": "artifacts/inositol-research/32839513.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ca10517672cac78ad8cdb0c593f14f73f1989e55977432d979690eebc3eefed", "start_char": 0, "end_char": 1711, "text_sha256": "5ca10517672cac78ad8cdb0c593f14f73f1989e55977432d979690eebc3eefed"} [ino-p32839513] Inositol monophosphatase 1 (IMPA1) mutation in intellectual disability patients impairs neurogenesis but not gliogenesis. (2021). https://pubmed.ncbi.nlm.nih.gov/32839513/ DOI: 10.1038/s41380-020-00862-9
Complete structured claim and evidence
Myo-inositol supplementation of differentiation medium rescued the reported neuronal-progenitor phenotype in IMPA1-deficient patient-derived cultures.
Myo-inositol → Neural progenitor survival and neurogenesis source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/inositol-research/32839513.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ca10517672cac78ad8cdb0c593f14f73f1989e55977432d979690eebc3eefed", "start_char": 0, "end_char": 1711, "text_sha256": "5ca10517672cac78ad8cdb0c593f14f73f1989e55977432d979690eebc3eefed"}
experimental_model
Patient-derived iPSC differentiation and rescue
exposure
Biallelic IMPA1 defect and myo-inositol-supplemented medium
limitations
Cellular rescue is not demonstrated neurological benefit in treated patients; effects were lineage-specific.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
Providing the missing downstream molecule helped cells in culture; clinical benefit remains untested here.
primary_references
[ino-p32839513] Inositol monophosphatase 1 (IMPA1) mutation in intellectual disability patients impairs neurogenesis but not gliogenesis. (2021). https://pubmed.ncbi.nlm.nih.gov/32839513/ DOI: 10.1038/s41380-020-00862-9
tissue_or_cell_type
Hippocampal dentate-gyrus-like neuronal progenitors
trigger_kind
machinery_impairment Imported condition classification; unverified.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1276–1287
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient-derived iPSC differentiation and rescue · source_derived_draft · unverified_draft
### ino-impa1-myo-rescue Myo-inositol supplementation of differentiation medium rescued the reported neuronal-progenitor phenotype in IMPA1-deficient patient-derived cultures. Condition category: machinery_impairment nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Providing the missing downstream molecule helped cells in culture; clinical benefit remains untested here. organism: Homo sapiens tissue_or_cell_type: Hippocampal dentate-gyrus-like neuronal progenitors experimental_model: Patient-derived iPSC differentiation and rescue limitations: Cellular rescue is not demonstrated neurological benefit in treated patients; effects were lineage-specific. exposure: Biallelic IMPA1 defect and myo-inositol-supplemented medium evidence_span: {"source_cache": "artifacts/inositol-research/32839513.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ca10517672cac78ad8cdb0c593f14f73f1989e55977432d979690eebc3eefed", "start_char": 0, "end_char": 1711, "text_sha256": "5ca10517672cac78ad8cdb0c593f14f73f1989e55977432d979690eebc3eefed"} [ino-p32839513] Inositol monophosphatase 1 (IMPA1) mutation in intellectual disability patients impairs neurogenesis but not gliogenesis. (2021). https://pubmed.ncbi.nlm.nih.gov/32839513/ DOI: 10.1038/s41380-020-00862-9
Complete structured claim and evidence
Recombinant human SULT1A1*2 converted indoxyl to indoxyl sulfate using PAPS; apparent indoxyl Km was 5.6 ± 1.8 micromolar.
Human sulfotransferase 1A1 / SULT1A1 → Indoxyl sulfate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human recombinant allozyme and liver cytosol kinetic comparison.
limitations
Sulfation does not necessarily make a retained metabolite harmless; no inference that sulfur intake controls clinical toxicity.
nutrient_topic
Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan
plain_language
A human sulfation enzyme adds a sulfur-containing group to the metabolite.
primary_references
Sulfation of indoxyl by human and rat aryl (phenol) sulfotransferases to form indoxyl sulfate. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12064372/ · DOI 10.1007/BF03190428
Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 594–600
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human recombinant allozyme and liver cytosol kinetic comparison. · source_derived_draft · unverified_draft
## tryptophan-indoxyl-sulfation A human sulfation enzyme adds a sulfur-containing group to the metabolite. Recombinant human SULT1A1*2 converted indoxyl to indoxyl sulfate using PAPS; apparent indoxyl Km was 5.6 ± 1.8 micromolar. Model: Human recombinant allozyme and liver cytosol kinetic comparison. Limitations: Sulfation does not necessarily make a retained metabolite harmless; no inference that sulfur intake controls clinical toxicity. Evidence access: Primary abstract Sulfation of indoxyl by human and rat aryl (phenol) sulfotransferases to form indoxyl sulfate. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12064372/ · DOI 10.1007/BF03190428
Complete structured claim and evidence
Eleven days of potassium deprivation reduced AQP2 abundance in rat cortical and medullary collecting ducts.
Potassium → Aquaporin-2 / AQP2 source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
endpoint
Eleven days of potassium deprivation reduced AQP2 abundance in rat cortical and medullary collecting ducts.
experimental-exposure
Rats with 11 days of potassium deprivation; AQP2 immunoblot/immunocytochemistry, urine volume, and potassium refeeding.
experimental_model
Rats with 11 days of potassium deprivation; AQP2 immunoblot/immunocytochemistry, urine volume, and potassium refeeding.
limitations
Parallel changes and refeeding support reversibility, but no AQP2-specific rescue isolated its complete contribution.
nutrient_topic
Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
organism
Rattus norvegicus
plain_language
Less water-channel protein accompanied the concentrating defect.
primary_references
[marples-1996-aqp2] Hypokalemia-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla and cortex (1996). https://pubmed.ncbi.nlm.nih.gov/8621781/ DOI: 10.1172/JCI118628
tissue_or_cell_type
cortical and inner medullary collecting ducts
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1386–1397
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rats with 11 days of potassium deprivation; AQP2 immunoblot/immunocytochemistry, urine volume, and potassium refeeding. · source_derived_draft · unverified_draft
### k-depletion-aqp2-abundance Eleven days of potassium deprivation reduced AQP2 abundance in rat cortical and medullary collecting ducts. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Less water-channel protein accompanied the concentrating defect. organism: Rattus norvegicus tissue_or_cell_type: cortical and inner medullary collecting ducts experimental_model: Rats with 11 days of potassium deprivation; AQP2 immunoblot/immunocytochemistry, urine volume, and potassium refeeding. limitations: Parallel changes and refeeding support reversibility, but no AQP2-specific rescue isolated its complete contribution. experimental-exposure: Rats with 11 days of potassium deprivation; AQP2 immunoblot/immunocytochemistry, urine volume, and potassium refeeding. endpoint: Eleven days of potassium deprivation reduced AQP2 abundance in rat cortical and medullary collecting ducts. [marples-1996-aqp2] Hypokalemia-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla and cortex (1996). https://pubmed.ncbi.nlm.nih.gov/8621781/ DOI: 10.1172/JCI118628
Complete structured claim and evidence
Dietary potassium restriction reduced Ser256-phosphorylated AQP2 in cortical and medullary collecting ducts of both male and female mice.
Potassium → Ser256-phosphorylated AQP2 source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
endpoint
Dietary potassium restriction reduced Ser256-phosphorylated AQP2 in cortical and medullary collecting ducts of both male and female mice.
experimental-exposure
Male and female C57BL/6J mice exposed to graded potassium restriction for eight days; water-balance and collecting-duct signaling measurements.
experimental_model
Male and female C57BL/6J mice exposed to graded potassium restriction for eight days; water-balance and collecting-duct signaling measurements.
limitations
Sex and segment influenced severity; this does not establish a universal human plasma-potassium threshold or a unique responsible kinase.
nutrient_topic
Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
organism
Mus musculus
plain_language
The channel activation/trafficking state changed even where total protein loss was less marked.
primary_references
[al-qusairi-2021-vasopressin] Rapid development of vasopressin resistance in dietary K+ deficiency (2021). https://pubmed.ncbi.nlm.nih.gov/33749322/ DOI: 10.1152/ajprenal.00655.2020
tissue_or_cell_type
cortical and medullary collecting duct
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1412–1423
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Male and female C57BL/6J mice exposed to graded potassium restriction for eight days; water-balance and collecting-duct signaling measurements. · source_derived_draft · unverified_draft
### k-restriction-lowers-aqp2-ser256 Dietary potassium restriction reduced Ser256-phosphorylated AQP2 in cortical and medullary collecting ducts of both male and female mice. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The channel activation/trafficking state changed even where total protein loss was less marked. organism: Mus musculus tissue_or_cell_type: cortical and medullary collecting duct experimental_model: Male and female C57BL/6J mice exposed to graded potassium restriction for eight days; water-balance and collecting-duct signaling measurements. limitations: Sex and segment influenced severity; this does not establish a universal human plasma-potassium threshold or a unique responsible kinase. experimental-exposure: Male and female C57BL/6J mice exposed to graded potassium restriction for eight days; water-balance and collecting-duct signaling measurements. endpoint: Dietary potassium restriction reduced Ser256-phosphorylated AQP2 in cortical and medullary collecting ducts of both male and female mice. [al-qusairi-2021-vasopressin] Rapid development of vasopressin resistance in dietary K+ deficiency (2021). https://pubmed.ncbi.nlm.nih.gov/33749322/ DOI: 10.1152/ajprenal.00655.2020
Complete structured claim and evidence
CaSR potentiation by NPS R-568 strengthens extracellular-calcium-mediated inhibition of PTH secretion in bovine parathyroid cells.
Calcium-sensing receptor / CaSR → Parathyroid hormone secretion source_derived_draftungraded
Experimental context and source evidence
experimental_model
Bovine parathyroid cells and human CaSR-expressing HEK293 cells
limitations
Pharmacological cell experiment; potentiation required extracellular calcium.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Bos taurus
plain_language
Greater calcium-sensor activation reduces hormone release.
primary_references
[nemeth1998] Calcimimetics with potent and selective activity on the parathyroid calcium receptor (1998). https://pmc.ncbi.nlm.nih.gov/articles/PMC19959/ DOI: 10.1073/pnas.95.7.4040
tissue_or_cell_type
Parathyroid cells
Calcium: mechanism-first literature curation (2026-09-17) · lines 25–34
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bovine parathyroid cells and human CaSR-expressing HEK293 cells · source_derived_draft · unverified_draft
### casr-calcium-pth-suppression CaSR potentiation by NPS R-568 strengthens extracellular-calcium-mediated inhibition of PTH secretion in bovine parathyroid cells. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Greater calcium-sensor activation reduces hormone release. organism: Bos taurus tissue_or_cell_type: Parathyroid cells experimental_model: Bovine parathyroid cells and human CaSR-expressing HEK293 cells limitations: Pharmacological cell experiment; potentiation required extracellular calcium. [nemeth1998] Calcimimetics with potent and selective activity on the parathyroid calcium receptor (1998). https://pmc.ncbi.nlm.nih.gov/articles/PMC19959/ DOI: 10.1073/pnas.95.7.4040
Complete structured claim and evidence
Combined Na/Mg restriction increased native ROMK activity in DCT2/CNT and lowered plasma K, while ENaC cleavage markers were preserved relative to normal diet.
Magnesium → Renal outer medullary potassium channel / KCNJ1 source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
magnesium -> sodium -> potassium
duration
Seven days
experimental_contrast
{"combination": "joint", "comparator": "Normal diet", "conditions": [{"entity_slug": "sodium", "state": "Restricted"}, {"entity_slug": "magnesium", "state": "Restricted"}], "effect_direction": "increase", "endpoint": "Native ROMK activity in DCT2/CNT", "intervention": "Combined dietary sodium and magnesium restriction"} Primary abstract PMID 41137719 / DOI 10.1113/JP287704 rechecked 2026-09-20. This comparison must not be separated into two single-deficiency effects.
experimental_model
Dietary restriction in C57BL/6J mice with renal transport assays
limitations
Co-occurrence supports the proposed mechanism; intracellular Mg and distal Na delivery were not directly measured.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Mus musculus
plain_language
In this combined shortage, the Mg-sensitive potassium pathway was more active while the sodium pathway that supports potassium exit remained available.
primary_references
[maeoka-2025-enac-romk] Hypomagnesaemia-associated hypokalaemia requires activation of both ENaC and ROMK (2025). https://pubmed.ncbi.nlm.nih.gov/41137719/ DOI: 10.1113/JP287704
tissue_or_cell_type
Kidney distal nephron
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 178–189
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary restriction in C57BL/6J mice with renal transport assays · source_derived_draft · unverified_draft
### combined-na-mg-restriction-romk-hypokalemia Combined Na/Mg restriction increased native ROMK activity in DCT2/CNT and lowered plasma K, while ENaC cleavage markers were preserved relative to normal diet. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this combined shortage, the Mg-sensitive potassium pathway was more active while the sodium pathway that supports potassium exit remained available. organism: Mus musculus tissue_or_cell_type: Kidney distal nephron experimental_model: Dietary restriction in C57BL/6J mice with renal transport assays limitations: Co-occurrence supports the proposed mechanism; intracellular Mg and distal Na delivery were not directly measured. cross_nutrient: magnesium -> sodium -> potassium duration: Seven days [maeoka-2025-enac-romk] Hypomagnesaemia-associated hypokalaemia requires activation of both ENaC and ROMK (2025). https://pubmed.ncbi.nlm.nih.gov/41137719/ DOI: 10.1113/JP287704
Complete structured claim and evidence

Availability and dependencies

Each situation shows the normal role first, then what the sources report under a specific condition. A shortfall in the diet, a fault in the machinery, and a low blood reading are kept separate because they are not the same thing.

PAP builds up when its clearance enzyme is absent

Condition: machinery_impairment · Genetic Bpnt1 deletion in mice.